David N Silverman

David N Silverman, Ph.D.

DIS PROFESSOR EMERITUS

Department: MD-PHARMACOLOGY / THERAPEUTICS
Business Phone: (352) 256-6908
Business Email: silvrmn@ufl.edu

Accomplishments

Chair
2004 · Gordon Conference on Isotopes in Biological and Chemical Sciences
Vice-chair
2002 · Gordon Conference on Isotopes in Biological and Chemical Sciences
Co-chair
2000 · International Conference on the Carbonic Anhydrases
Honorary doctorate
1997 · Umea University, Sweden
Co-chair
1995 · Gordon Conference on Enzymes, Coenzymes, and Metabolic Pathways
Member
1992-1996 · Physical Biochemistry Study Section, NIH
Basic Research Prize
1984 · 25th Anniversary of the University of Florida College of Medicine
Teacher of the Year
1982-1983 · University of Florida College of Medicine

Teaching Profile

Courses Taught
2014
MDU4002 Introduction to Medical Science Seminar 2
2013
BMS6031 Foundations of Med
2011-2013
DEN6262 Prin of Pharmacology
2006-2009,2011
GMS6563 Molecular Pharmacology

Research Profile

Dr. Silverman’s lab studied the catalytic mechanism of two very fast enzymes, carbonic anhydrase and superoxide dismutase. They asked what accounts for the extraordinary efficiency of these enzymes, which are able to convert the substrates carbon dioxide and superoxide to products with catalytic turnovers as great as one million per second. Both enzymes are involved in critical physiological processes. The carbonic anhydrases comprise many isoforms in humans that convert carbon dioxide into bicarbonate to form secretory fluids and in the red cells’ function during respiration. The superoxide dismutases convert superoxide, a toxic by-product of many enzymatic reactions, into hydrogen peroxide and oxygen.

With carbonic anhydrase, their work focused mainly on the mechanism of proton transfer in the active site. In the pathway, protons must be transferred from the zinc-bound water to solution at a rate at least as fast as a million per second. There is a proton shuttle residue, His64 in many carbonic anhydrase isozymes, that accepts a proton from the zinc-bound water through intervening hydrogen-bonded water bridges and transfers it to the solution. They measured the rates of intramolecular proton transfer in many isozymes and site-specific mutants of carbonic anhydrase to understand what processes determine the activation barrier for this proton transfer rate. Among the possibilities are the energy to orient side chains, such as His64, and the energy to form a hydrogen-bonded water chain between the zinc and His64. This is a very good system for studying such proton transfers, and the properties of intramolecular proton transfer that they discovered should be applicable to more complex systems such as bacteriorhodopsin, cytochrome c oxidase, and F0F1 ATPase, among others.

Their work with manganese superoxide dismutase was, in some ways, similar to that on carbonic anhydrase to determine the pathway and rates of the proton transfers that form the product hydrogen peroxide. This enzyme has a network of hydrogen-bonded water and side chains that extend throughout the active site. Their work with site-specific mutants determined that this network plays a critical role in these proton transfers. They also studied the role of nearby residues on the redox potential of the manganese and how this influences the catalysis. Under many conditions, manganese superoxide dismutase is limited in rate by a product inhibition. Using a variety of methods, they measured the rates of formation of the inhibited complex and identified its structure.

Much of their work involved measuring the rates of very fast enzymatic reactions. They used several methods in their work on carbonic anhydrase and superoxide dismutase. Stopped-flow spectrophotometry is capable of measuring the optical properties of solutions containing enzyme and substrate after a mixing time of about 1.5 milliseconds. Their instrumentation could measure a full absorption spectrum about every millisecond after that. With superoxide dismutase, reactions are often faster than that, in which case they used pulse radiolysis which relies on an electron accelerator at the Brookhaven National Laboratory. They also found that mass spectrometry to measure the enzyme catalyzed exchange of oxygen-18 between carbon dioxide and water is very informative for carbonic anhydrase. Through collaborations, they had projects to determine structure using x-ray diffraction and to determine the properties of the manganese using electron paramagnetic resonance, as well as studies of stabilities using scanning differential calorimetry.

Publications

2018
Carbonic anhydrase II does not exhibit Nitrite reductase or Nitrous Anhydrase Activity.
Free radical biology & medicine. 117:1-5 [DOI] 10.1016/j.freeradbiomed.2018.01.015. [PMID] 29355738.
2016
Substrate Binding Mode and Molecular Basis of a Specificity Switch in Oxalate Decarboxylase.
Biochemistry. 55(14):2163-73 [DOI] 10.1021/acs.biochem.6b00043. [PMID] 27014926.
2015
Activity and anion inhibition studies of the α-carbonic anhydrase from Thiomicrospira crunogena XCL-2 Gammaproteobacterium.
Bioorganic & medicinal chemistry letters. 25(21):4937-4940 [DOI] 10.1016/j.bmcl.2015.05.001. [PMID] 25998503.
2015
NMR studies of active-site properties of human carbonic anhydrase II by using (15) N-labeled 4-methylimidazole as a local probe and histidine hydrogen-bond correlations.
Chemistry (Weinheim an der Bergstrasse, Germany). 21(7):2915-29 [DOI] 10.1002/chem.201404083. [PMID] 25521423.
2015
Structural and biophysical characterization of the α-carbonic anhydrase from the gammaproteobacterium Thiomicrospira crunogena XCL-2: insights into engineering thermostable enzymes for CO2 sequestration.
Acta crystallographica. Section D, Biological crystallography. 71(Pt 8):1745-56 [DOI] 10.1107/S1399004715012183. [PMID] 26249355.
2014
Catalytic mechanism of α-class carbonic anhydrases: CO2 hydration and proton transfer.
Sub-cellular biochemistry. 75:31-52 [DOI] 10.1007/978-94-007-7359-2_3. [PMID] 24146373.
2014
Human carbonic anhydrase II-cyanate inhibitor complex: putting the debate to rest.
Acta crystallographica. Section F, Structural biology communications. 70(Pt 10):1324-7 [DOI] 10.1107/S2053230X14018135. [PMID] 25286933.
2014
Structural insight into activity enhancement and inhibition of H64A carbonic anhydrase II by imidazoles.
IUCrJ. 1(Pt 2):129-35 [DOI] 10.1107/S2052252514004096. [PMID] 25075329.
2013
Effects of cryoprotectants on the structure and thermostability of the human carbonic anhydrase II-acetazolamide complex.
Acta crystallographica. Section D, Biological crystallography. 69(Pt 5):860-5 [DOI] 10.1107/S0907444913002771. [PMID] 23633596.
2013
Investigating the Functional Importance of Active Site Loop Residues in Switching the Reactivity of the Mn(Ii) Center in Oxalate Decarboxylase
. 246
2013
Role of Trp19 and Tyr200 in catalysis by the γ-class carbonic anhydrase from Methanosarcina thermophila.
Archives of biochemistry and biophysics. 529(1):11-7 [DOI] 10.1016/j.abb.2012.10.010. [PMID] 23111186.
2013
Structural and catalytic characterization of a thermally stable and acid-stable variant of human carbonic anhydrase II containing an engineered disulfide bond.
Acta crystallographica. Section D, Biological crystallography. 69(Pt 8):1414-22 [DOI] 10.1107/S0907444913008743. [PMID] 23897465.
2013
Structural, catalytic and stabilizing consequences of aromatic cluster variants in human carbonic anhydrase II.
Archives of biochemistry and biophysics. 539(1):31-7 [DOI] 10.1016/j.abb.2013.09.001. [PMID] 24036123.
2013
Water networks in fast proton transfer during catalysis by human carbonic anhydrase II.
Biochemistry. 52(1):125-31 [DOI] 10.1021/bi301099k. [PMID] 23215152.
2012
Effect of Zinc On Carbonic Anhydrase Ix Activity in Mda-Mb-231 Breast Cancer Cells
The FASEB's Journal. 26
2012
Kinetic and structural characterization of thermostabilized mutants of human carbonic anhydrase II.
Protein engineering, design & selection : PEDS. 25(7):347-55 [DOI] 10.1093/protein/gzs027. [PMID] 22691706.
2012
Neutron diffraction of acetazolamide-bound human carbonic anhydrase II reveals atomic details of drug binding.
Journal of the American Chemical Society. 134(36):14726-9 [DOI] 10.1021/ja3068098. [PMID] 22928733.
2012
Role of zinc in catalytic activity of carbonic anhydrase IX.
Archives of biochemistry and biophysics. 521(1-2):90-4 [DOI] 10.1016/j.abb.2012.03.017. [PMID] 22465027.
2012
Structural and kinetic effects on changes in the CO(2) binding pocket of human carbonic anhydrase II.
Biochemistry. 51(45):9156-63 [DOI] 10.1021/bi301155z. [PMID] 23098192.
2011
Aqueous measurement of nitric oxide using membrane inlet membrane inlet mass spectrometry.
Methods in molecular biology (Clifton, N.J.). 704:105-14 [DOI] 10.1007/978-1-61737-964-2_9. [PMID] 21161633.
2011
Catalysis and pH control by membrane-associated carbonic anhydrase IX in MDA-MB-231 breast cancer cells.
The Journal of biological chemistry. 286(18):15789-96 [DOI] 10.1074/jbc.M110.188524. [PMID] 21454639.
2011
Chemical rescue of enzymes: proton transfer in mutants of human carbonic anhydrase II.
Journal of the American Chemical Society. 133(16):6223-34 [DOI] 10.1021/ja1097594. [PMID] 21452838.
2011
Detection of nitroxyl (HNO) by membrane inlet mass spectrometry.
Free radical biology & medicine. 50(10):1274-9 [DOI] 10.1016/j.freeradbiomed.2011.02.008. [PMID] 21349325.
2011
Intrinsic proton-donating power of zinc-bound water in a carbonic anhydrase active site model estimated by NMR.
Journal of the American Chemical Society. 133(29):11331-8 [DOI] 10.1021/ja203478j. [PMID] 21682342.
2011
Kinetic and crystallographic studies of the role of tyrosine 7 in the active site of human carbonic anhydrase II.
Archives of biochemistry and biophysics. 506(2):181-7 [DOI] 10.1016/j.abb.2010.12.004. [PMID] 21145876.
2011
Membrane inlet for mass spectrometric measurement of catalysis by enzymatic decarboxylases.
Analytical biochemistry. 418(1):73-7 [DOI] 10.1016/j.ab.2011.06.031. [PMID] 21782782.
2011
Neutron structure of human carbonic anhydrase II: a hydrogen-bonded water network “switch” is observed between pH 7.8 and 10.0.
Biochemistry. 50(44):9421-3 [DOI] 10.1021/bi201487b. [PMID] 21988105.
2011
Nitric oxide reversibly inhibits Bacillus subtilis oxalate decarboxylase.
Chemical communications (Cambridge, England). 47(11):3111-3 [DOI] 10.1039/c0cc04946h. [PMID] 21264418.
2011
Role of hypoxia and EGF on expression, activity, localization and phosphorylation of carbonic anhydrase IX in MDA-MB-231 breast cancer cells.
Biochimica et biophysica acta. 1813(1):159-67 [DOI] 10.1016/j.bbamcr.2010.09.018. [PMID] 20920536.
2011
Structure and catalysis by carbonic anhydrase II: role of active-site tryptophan 5.
Archives of biochemistry and biophysics. 516(2):97-102 [DOI] 10.1016/j.abb.2011.09.011. [PMID] 22001224.
2010
A Comparison of Membrane Inlet Mass Spectrometry and Nitric Oxide (No) Electrode Techniques To Detect No in Aqueous Solution
Electroanalysis. 22(4):445-448 [DOI] 10.1002/elan.200900407.
2010
A short, strong hydrogen bond in the active site of human carbonic anhydrase II.
Biochemistry. 49(2):249-51 [DOI] 10.1021/bi902007b. [PMID] 20000378.
2010
Comparison of solution and crystal properties of Co(II)-substituted human carbonic anhydrase II.
Archives of biochemistry and biophysics. 502(1):53-9 [DOI] 10.1016/j.abb.2010.07.010. [PMID] 20637176.
2010
Detecting extracellular carbonic anhydrase activity using membrane inlet mass spectrometry.
Analytical biochemistry. 403(1-2):74-8 [DOI] 10.1016/j.ab.2010.04.019. [PMID] 20417171.
2010
Enzymatic catalysis with rapid turnover-carbonic anhydrase and superoxide dismutase. Preface.
Biochimica et biophysica acta. 1804(2):243-4 [DOI] 10.1016/j.bbapap.2009.12.015. [PMID] 20129395.
2010
Enzymes for carbon sequestration: neutron crystallographic studies of carbonic anhydrase.
Acta crystallographica. Section D, Biological crystallography. 66(Pt 11):1178-83 [DOI] 10.1107/S0907444910019700. [PMID] 21041933.
2010
Inhibitory Mechanism of Nitric Oxide On Oxalate Decarboxylase
Free Radical Biology and Medicine. 49 [DOI] 10.1016/j.freeradbiomed.2010.10.309.
2010
Neutron structure of human carbonic anhydrase II: implications for proton transfer.
Biochemistry. 49(3):415-21 [DOI] 10.1021/bi901995n. [PMID] 20025241.
2010
Proton transfer in catalysis and the role of proton shuttles in carbonic anhydrase.
Biochimica et biophysica acta. 1804(2):422-6 [DOI] 10.1016/j.bbapap.2009.08.003. [PMID] 19679199.
2010
Reactions of nitrite in erythrocyte suspensions measured by membrane inlet mass spectrometry.
Free radical biology & medicine. 48(2):325-31 [DOI] 10.1016/j.freeradbiomed.2009.11.003. [PMID] 19913092.
2010
Structural and kinetic study of the extended active site for proton transfer in human carbonic anhydrase II.
Biochemistry. 49(30):6394-9 [DOI] 10.1021/bi1007645. [PMID] 20578724.
2009
Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in protein structure, stability, and solvent network.
Biochemistry. 48(31):7365-72 [DOI] 10.1021/bi9007512. [PMID] 19583303.
2009
Contribution of human manganese superoxide dismutase tyrosine 34 to structure and catalysis.
Biochemistry. 48(15):3417-24 [DOI] 10.1021/bi8023288. [PMID] 19265433.
2009
Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties.
Biochemistry. 48(6):1322-31 [DOI] 10.1021/bi802035f. [PMID] 19170619.
2009
Effect of active-site mutation at Asn67 on the proton transfer mechanism of human carbonic anhydrase II.
Biochemistry. 48(33):7996-8005 [DOI] 10.1021/bi901037u. [PMID] 19634894.
2009
Elucidation of the proton transport mechanism in human carbonic anhydrase II.
Journal of the American Chemical Society. 131(22):7598-608 [DOI] 10.1021/ja8091938. [PMID] 19438233.
2009
Expression and activity of carbonic anhydrase IX is associated with metabolic dysfunction in MDA-MB-231 breast cancer cells.
Cancer investigation. 27(6):613-23 [DOI] 10.1080/07357900802653464. [PMID] 19367501.
2009
Preliminary joint neutron and X-ray crystallographic study of human carbonic anhydrase II.
Acta crystallographica. Section F, Structural biology and crystallization communications. 65(Pt 5):495-8 [DOI] 10.1107/S1744309109013086. [PMID] 19407386.
2009
Reactions of Nitrite in Erythrocyte Suspensions Measured By Membrane Inlet Mass Spectrometry
Nitric Oxide-Biology and Chemistry. 20
2009
Reactions of nitrite with hemoglobin measured by membrane inlet mass spectrometry.
Free radical biology & medicine. 46(1):14-9 [DOI] 10.1016/j.freeradbiomed.2008.09.016. [PMID] 18848984.
2009
Role of the orbitofrontal cortex and dorsal striatum in regulating the dose-related effects of self-administered cocaine.
Behavioural brain research. 201(1):128-36 [DOI] 10.1016/j.bbr.2009.02.002. [PMID] 19428626.
2008
Combined NMR and computational study for azide binding to human manganese superoxide dismutase.
Solid state nuclear magnetic resonance. 34(1-2):6-13 [DOI] 10.1016/j.ssnmr.2008.03.005. [PMID] 18420387.
2008
Entrapment of carbon dioxide in the active site of carbonic anhydrase II.
The Journal of biological chemistry. 283(45):30766-71 [DOI] 10.1074/jbc.M805353200. [PMID] 18768466.
2008
Inhibition of carbonic anhydrase II by thioxolone: a mechanistic and structural study.
Biochemistry. 47(10):3174-84 [DOI] 10.1021/bi702385k. [PMID] 18266323.
2008
Origins of enhanced proton transport in the Y7F mutant of human carbonic anhydrase II.
Journal of the American Chemical Society. 130(34):11399-408 [DOI] 10.1021/ja802264j. [PMID] 18671353.
2008
Role of a glutamate bridge spanning the dimeric interface of human manganese superoxide dismutase.
Biochemistry. 47(16):4621-8 [DOI] 10.1021/bi7024518. [PMID] 18373354.
2008
Role of hydrophilic residues in proton transfer during catalysis by human carbonic anhydrase II.
Biochemistry. 47(46):12028-36 [DOI] 10.1021/bi801473w. [PMID] 18942852.
2008
The kinetic mechanism of manganese-containing superoxide dismutase from Deinococcus radiodurans: a specialized enzyme for the elimination of high superoxide concentrations.
Biochemistry. 47(8):2350-6 [DOI] 10.1021/bi7016206. [PMID] 18247479.
2007
Atomic crystal and molecular dynamics simulation structures of human carbonic anhydrase II: insights into the proton transfer mechanism.
Biochemistry. 46(11):2930-7 [PMID] 17319692.
2007
Location of binding sites in small molecule rescue of human carbonic anhydrase II.
Biophysical journal. 92(2):562-70 [PMID] 17071654.
2007
Membrane inlet for mass spectrometric measurement of nitric oxide.
Free radical biology & medicine. 43(10):1453-7 [PMID] 17936190.
2007
Nuclear magnetic resonance and ab initio studies of small complexes formed between water and pyridine derivatives in solid and liquid phases.
The journal of physical chemistry. A. 111(27):6084-93 [PMID] 17579378.
2007
Solvent-mediated proton transfer in catalysis by carbonic anhydrase.
Accounts of chemical research. 40(8):669-75 [PMID] 17550224.
2007
Speeding up proton transfer in a fast enzyme: kinetic and crystallographic studies on the effect of hydrophobic amino acid substitutions in the active site of human carbonic anhydrase II.
Biochemistry. 46(12):3803-13 [PMID] 17330962.
2007
Structural and kinetic analysis of proton shuttle residues in the active site of human carbonic anhydrase III.
Proteins. 68(1):337-43 [PMID] 17427958.
2007
Structural and kinetic study of differences between human and Escherichia coli manganese superoxide dismutases.
Biochemistry. 46(51):14830-7 [PMID] 18044968.
2006
Crystal structure of nitrated human manganese superoxide dismutase: mechanism of inactivation.
Free radical biology & medicine. 40(3):453-8 [PMID] 16443160.
2006
Engineering and characterization of human manganese superoxide dismutase mutants with high activity and low product inhibition.
The FEBS journal. 273(21):4853-61 [PMID] 16999822.
2006
Expression, purification, kinetic, and structural characterization of an alpha-class carbonic anhydrase from Aedes aegypti (AaCA1).
Biochimica et biophysica acta. 1764(8):1413-9 [PMID] 16920039.
2006
Production and X-ray crystallographic analysis of fully deuterated human carbonic anhydrase II.
Acta crystallographica. Section F, Structural biology and crystallization communications. 62(Pt 1):6-9 [PMID] 16511248.
2006
Structural mobility in human manganese superoxide dismutase.
Biochemistry. 45(27):8209-15 [PMID] 16819819.
2006
Structure of human salivary alpha-amylase crystallized in a C-centered monoclinic space group.
Acta crystallographica. Section F, Structural biology and crystallization communications. 62(Pt 2):88-93 [PMID] 16511271.
2006
X-ray crystallographic studies reveal that the incorporation of spacer groups in carbonic anhydrase inhibitors causes alternate binding modes.
Acta crystallographica. Section F, Structural biology and crystallization communications. 62(Pt 7):618-22 [PMID] 16820676.
2005
Carbonic anhydrase in the adult mosquito midgut.
The Journal of experimental biology. 208(Pt 17):3263-73 [PMID] 16109888.
2005
Exchange of (18)O in the reaction of peroxynitrite with CO(2).
Free radical biology & medicine. 38(1):93-7 [PMID] 15589376.
2005
Human carbonic anhydrase III: structural and kinetic study of catalysis and proton transfer.
Biochemistry. 44(30):10046-53 [PMID] 16042381.
2005
Hydrogen bonding in human manganese superoxide dismutase containing 3-fluorotyrosine.
Biophysical journal. 89(6):4171-9 [PMID] 16150974.
2005
Proton transfer from exogenous donors in catalysis by human carbonic anhydrase II.
Archives of biochemistry and biophysics. 437(1):106-14 [PMID] 15820222.
2005
Proton transfer in a Thr200His mutant of human carbonic anhydrase II.
Proteins. 61(2):239-45 [PMID] 16106378.
2005
Structural and kinetic characterization of active-site histidine as a proton shuttle in catalysis by human carbonic anhydrase II.
Biochemistry. 44(4):1097-105 [PMID] 15667203.
2004
Activation of carbonic anhydrase II by active-site incorporation of histidine analogs.
Archives of biochemistry and biophysics. 421(2):283-9 [PMID] 14984209.
2004
Alkalization of larval mosquito midgut and the role of carbonic anhydrase in different species of mosquitoes.
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. 137(3):207-25 [PMID] 15171946.
2004
Amino acid substitution at the dimeric interface of human manganese superoxide dismutase.
The Journal of biological chemistry. 279(7):5861-6 [PMID] 14638684.
2004
Potent anti-tumor effects of an active site mutant of human manganese-superoxide dismutase. Evolutionary conservation of product inhibition.
The Journal of biological chemistry. 279(13):12769-76 [PMID] 14688256.
2004
Role of hydrogen bonding in the active site of human manganese superoxide dismutase.
Biochemistry. 43(22):7038-45 [PMID] 15170341.
2003
Catalytic and structural effects of amino acid substitution at histidine 30 in human manganese superoxide dismutase: insertion of valine C gamma into the substrate access channel.
Biochemistry. 42(10):2781-9 [PMID] 12627943.
2003
The refined atomic structure of carbonic anhydrase II at 1.05 A resolution: implications of chemical rescue of proton transfer.
Acta crystallographica. Section D, Biological crystallography. 59(Pt 1):93-104 [PMID] 12499545.
2003
Using evolutionary rates to investigate protein functional divergence and conservation. A case study of the carbonic anhydrases.
Genetics. 164(4):1261-9 [PMID] 12930737.
2002
Catalytic pathway of manganese superoxide dismutase by direct observation of superoxide.
Methods in enzymology. 349:61-74 [PMID] 11912930.
2002
Chemical rescue in catalysis by human carbonic anhydrases II and III.
Biochemistry. 41(9):3235-42 [PMID] 11863462.
2002
Chemical rescue of proton transfer in catalysis by carbonic anhydrases in the beta- and gamma-class.
Biochemistry. 41(51):15429-35 [PMID] 12484784.
2002
Kinetic analysis of multiple proton shuttles in the active site of human carbonic anhydrase.
The Journal of biological chemistry. 277(41):38870-6 [PMID] 12171926.
2002
Proton transfer within the active-site cavity of carbonic anhydrase III.
Biochimica et biophysica acta. 1599(1-2):21-7 [PMID] 12484342.
2001
Bicarbonate as a proton donor in catalysis by Zn(II)- and Co(II)-containing carbonic anhydrases.
Journal of the American Chemical Society. 123(25):5861-6 [PMID] 11414818.
2001
Structural and kinetic analysis of the chemical rescue of the proton transfer function of carbonic anhydrase II.
Biochemistry. 40(6):1741-8 [PMID] 11327835.
2000
Enhancement of catalytic efficiency by the combination of site-specific mutations in a carbonic anhydrase-related protein.
European journal of biochemistry. 267(19):5908-15 [PMID] 10998050.
2000
Marcus rate theory applied to enzymatic proton transfer.
Biochimica et biophysica acta. 1458(1):88-103 [PMID] 10812026.
2000
Multiple replacements of glutamine 143 in human manganese superoxide dismutase: effects on structure, stability, and catalysis.
Biochemistry. 39(24):7131-7 [PMID] 10852710.
2000
Purification and kinetic analysis of recombinant CA XII, a membrane carbonic anhydrase overexpressed in certain cancers.
Proceedings of the National Academy of Sciences of the United States of America. 97(26):14212-7 [PMID] 11121027.
2000
The catalytic mechanism of mammalian carbonic anhydrases.
EXS. (90):175-95 [PMID] 11268516.
1999
Application of Marcus rate theory to proton transfer in enzyme-catalyzed reactions.
Methods in enzymology. 308:276-97 [PMID] 10507009.
1999
Carbon dioxide transport by proteic and facilitated transport membranes.
Life support & biosphere science : international journal of earth space. 6(4):293-302 [PMID] 11543269.
1999
Characterization of the product-inhibited complex in catalysis by human manganese superoxide dismutase.
The Journal of biological chemistry. 274(35):24457-60 [PMID] 10455106.
1999
Interrupting the hydrogen bond network at the active site of human manganese superoxide dismutase.
The Journal of biological chemistry. 274(39):27711-6 [PMID] 10488113.
1999
Introduction of histidine analogs leads to enhanced proton transfer in carbonic anhydrase V.
Archives of biochemistry and biophysics. 361(2):264-70 [PMID] 9882455.
1999
Kinetic and spectroscopic characterization of the gamma-carbonic anhydrase from the methanoarchaeon Methanosarcina thermophila.
Biochemistry. 38(40):13119-28 [PMID] 10529183.
1999
Proton transfer to residues of basic pK(a) during catalysis by carbonic anhydrase.
Biochimica et biophysica acta. 1434(1):1-5 [PMID] 10556554.
1999
Role of tryptophan 161 in catalysis by human manganese superoxide dismutase.
Biochemistry. 38(36):11686-92 [PMID] 10512624.
1998
Crystal structure of Y34F mutant human mitochondrial manganese superoxide dismutase and the functional role of tyrosine 34.
Biochemistry. 37(14):4722-30 [PMID] 9537987.
1998
Intramolecular proton transfer from multiple sites in catalysis by murine carbonic anhydrase V.
Biochemistry. 37(20):7649-55 [PMID] 9585580.
1998
Probing the active site of human manganese superoxide dismutase: the role of glutamine 143.
Biochemistry. 37(14):4731-9 [PMID] 9537988.
1998
Properties of intramolecular proton transfer in carbonic anhydrase III.
Biophysical journal. 74(6):3182-9 [PMID] 9635771.
1998
Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: molecular basis of isozyme-drug discrimination.
Protein science : a publication of the Protein Society. 7(3):556-63 [PMID] 9541386.
1998
The catalytic properties of murine carbonic anhydrase VII.
Biochemistry. 37(30):10837-45 [PMID] 9692974.
1997
Catalytic properties of murine carbonic anhydrase IV.
The Journal of biological chemistry. 272(21):13512-8 [PMID] 9153196.
1997
Glutamate and aspartate as proton shuttles in mutants of carbonic anhydrase.
Biochemistry. 36(50):15758-64 [PMID] 9398305.
1996
Catalytic properties of human manganese superoxide dismutase.
The Journal of biological chemistry. 271(30):17687-91 [PMID] 8663465.
1996
Structure-based design of an intramolecular proton transfer site in murine carbonic anhydrase V.
Biochemistry. 35(36):11605-11 [PMID] 8794740.
1995
Proton transfer by histidine 67 in site-directed mutants of human carbonic anhydrase III.
Biochemistry. 34(26):8492-8 [PMID] 7599138.
1995
Proton transfer in carbonic anhydrase measured by equilibrium isotope exchange.
Methods in enzymology. 249:479-503 [PMID] 7791624.
1995
Structure determination of murine mitochondrial carbonic anhydrase V at 2.45-A resolution: implications for catalytic proton transfer and inhibitor design.
Proceedings of the National Academy of Sciences of the United States of America. 92(24):10949-53 [PMID] 7479916.
1994
Catalytic properties of mouse carbonic anhydrase V.
The Journal of biological chemistry. 269(40):24742-6 [PMID] 7929150.
1994
Comparison of intra- and intermolecular proton transfer in human carbonic anhydrase II.
The Journal of biological chemistry. 269(27):17988-92 [PMID] 8027057.
1994
Interactions of active-site residues and catalytic activity of human carbonic anhydrase III.
The Journal of biological chemistry. 269(37):23002-6 [PMID] 8083199.
1993
A physiological role for cyanate-induced carbonic anhydrase in Escherichia coli.
Journal of bacteriology. 175(5):1443-51 [PMID] 8444806.
1993
Influence of amino acid replacement at position 198 on catalytic properties of zinc-bound water in human carbonic anhydrase III.
Biochemistry. 32(22):5786-91 [PMID] 8504098.
1993
Interaction and influence of phenylalanine-198 and threonine-199 on catalysis by human carbonic anhydrase III.
Biochemistry. 32(31):7861-5 [PMID] 8347590.
1993
Kinetic analysis of a mutant (His107–>Tyr) responsible for human carbonic anhydrase II deficiency syndrome.
The Journal of biological chemistry. 268(7):4775-9 [PMID] 8444854.
1993
Rate-equilibria relationships in intramolecular proton transfer in human carbonic anhydrase III.
Biochemistry. 32(40):10757-62 [PMID] 8399223.
1992
A T7 expression vector optimized for site-directed mutagenesis using oligodeoxyribonucleotide cassettes.
Gene. 117(1):113-7 [PMID] 1644301.
1992
Catalysis by mutants of human carbonic anhydrase II: effects of replacing hydrophobic residues 198 and 204.
Biochimica et biophysica acta. 1159(3):274-8 [PMID] 1327160.
1991
Catalytic enhancement of human carbonic anhydrase III by replacement of phenylalanine-198 with leucine.
Biochemistry. 30(34):8463-70 [PMID] 1909176.
1991
Enhancement of the catalytic properties of human carbonic anhydrase III by site-directed mutagenesis.
Biochemistry. 30(6):1484-90 [PMID] 1899618.
1990
Buffer enhancement of proton transfer in catalysis by human carbonic anhydrase III.
Biochemistry. 29(27):6400-5 [PMID] 2169869.
1990
Enhancement of the catalytic activity of carbonic anhydrase III by phosphates.
The Journal of biological chemistry. 265(36):22270-4 [PMID] 2125046.
1989
Chemical modification of carbonic anhydrase II with acrolein.
The Journal of biological chemistry. 264(21):12389-93 [PMID] 2501305.
1989
Role of histidine 64 in the catalytic mechanism of human carbonic anhydrase II studied with a site-specific mutant.
Biochemistry. 28(19):7913-8 [PMID] 2514797.
1987
Carbonic Anhydrase and the Uptake of Inorganic Carbon by Synechococcus sp. (UTEX-2380).
Plant physiology. 85(1):72-7 [PMID] 16665686.
1986
Hydrolysis of 4-nitrophenyl acetate catalyzed by carbonic anhydrase III from bovine skeletal muscle.
The Journal of biological chemistry. 261(22):10100-3 [PMID] 3090030.
1986
Molecular basis of the oxygen exchange from CO2 catalyzed by carbonic anhydrase III from bovine skeletal muscle.
Biochemistry. 25(26):8402-8 [PMID] 3103674.
1986
Observation of the visible absorption spectrum of cobalt(II)-carbonic anhydrase III during catalytic hydration of carbon dioxide.
Journal of the American Chemical Society. 108(19):6065-6 [DOI] 10.1021/ja00279a079. [PMID] 22175387.
1986
Oxygen-18 Exchange as a Measure of Accessibility of CO(2) and HCO(3) to Carbonic Anhydrase in Chlorella vulgaris (UTEX 263).
Plant physiology. 80(4):997-1001 [PMID] 16664755.
1985
Catalysis by cobalt(II)-substituted carbonic anhydrase II of the exchange of oxygen-18 between CO2 and H2O.
Biochemistry. 24(21):5881-7 [PMID] 3936538.
1985
Inhibition of the hydration of CO2 catalyzed by carbonic anhydrase III from cat muscle.
The Journal of biological chemistry. 260(6):3484-9 [PMID] 3919025.
1985
Oxidation in H2O and D2O of 6-ethyl-5H-dibenz(c,e)azepine and 1-methylnicotinamide by aldehyde oxidase from rabbit liver.
Archives of biochemistry and biophysics. 241(2):649-55 [PMID] 2994572.
1984
Design and methods in a multi-center case-control interview study.
American journal of public health. 74(1):52-6 [PMID] 6689843.
1984
Kinetics of the hydration of CO2 catalyzed by carbonic anhydrase III from skeletal muscle of the cat.
Annals of the New York Academy of Sciences. 429:129-36 [PMID] 6430148.
1984
Purification and characterization of carbonic anhydrase from the saliva of the rat.
The Journal of biological chemistry. 259(9):5447-53 [PMID] 6425289.
1983
Proton transfer in the catalytic mechanism of carbonic anhydrase.
CRC critical reviews in biochemistry. 14(3):207-55 [PMID] 6313293.
1983
The pH dependence of the hydration of CO2 catalyzed by carbonic anhydrase III from skeletal muscle of the cat. Steady state and equilibrium studies.
The Journal of biological chemistry. 258(14):8867-71 [PMID] 6408094.
1982
Carbonic anhydrase activity in mitochondria from rat liver.
The Journal of biological chemistry. 257(12):6850-5 [PMID] 6806256.
1982
Carbonic anhydrase: oxygen-18 exchange catalyzed by an enzyme with rate-contributing proton-transfer steps.
Methods in enzymology. 87:732-52 [PMID] 6294458.
1982
Solvent deuterium isotope effects in the catalysis of oxygen-18 exchange by human carbonic anhydrase II.
Biochemistry. 21(25):6353-60 [PMID] 6817788.
1981
Diffusion-limited exchange of 18O between CO2 and water in red cell suspensions.
Respiration physiology. 44(3):285-98 [PMID] 6791257.
1981
Inhibition by cupric ions of 18O exchange catalyzed by human carbonic anhydrase II. Relation to the interaction between carbonic anhydrase and hemoglobin.
The Journal of biological chemistry. 256(18):9466-70 [PMID] 6793570.
1980
Carbon dioxide hydration activity of carbonic anhydrase in mixtures of water and deuterium oxide.
Biochemistry. 19(22):4984-9 [PMID] 6779860.
1980
The carbon dioxide hydration activity of brush-border carbonic anhydrase from the dog kidney.
Archives of biochemistry and biophysics. 205(1):51-6 [PMID] 6255876.
1979
Role of hemoglobin in proton transfer to the active site of carbonic anhydrase.
The Journal of biological chemistry. 254(8):2588-91 [PMID] 107161.
1978
CO2 kinetics in red cell suspensions measured by 18O exchange.
The Journal of biological chemistry. 253(22):8178-84 [PMID] 711742.
1978
Proton transfer between hemoglobin and the carbonic anhydrase active site.
The Journal of biological chemistry. 253(8):2563-7 [PMID] 416031.
1976
Carbonic anhydrase catalyzed hydration studied by 13C and 18O labeling of carbon dioxide.
Journal of the American Chemical Society. 98(4):978-84 [PMID] 812897.
1976
Depletion of 18O from C18O2 in erythrocyte suspensions. The permeability of the erythrocyte membrane to CO2.
The Journal of biological chemistry. 251(14):4428-35 [PMID] 932039.
1975
Letter: The mechanism of carbonic anhydrase studied by 13C and 18Q labeling of carbon dioxide.
Journal of the American Chemical Society. 97(20):5935-6 [PMID] 239984.
1973
Carbonic anhydrase catalyzed oxygen-18 exchange between bicarbonate and water.
Archives of biochemistry and biophysics. 155(2):452-7 [PMID] 4196184.
1973
The detection and localization of carbonic anhydrase in the rabbit cornea.
Experimental eye research. 17(2):129-36 [PMID] 4202414.
1972
Hairpin bend and interhelical interactions in -helical poly(L-alanine) in water.
Archives of biochemistry and biophysics. 153(2):449-56 [PMID] 4662091.
1972
Nuclearmagnetic resonance study of the N-terminal fragment of bovine pancreatic ribonuclease.
Archives of biochemistry and biophysics. 150(2):757-66 [PMID] 5065142.
1971
Nuclear magnetic resonance studies of side-chain interactions in polyamino acids with aromatic groups. Comparison to conformational energy calculations.
Biochemistry. 10(8):1340-7 [PMID] 5580655.
1971
Nuclear magnetic resonance study of the side-chain conformation of -helical poly- -benzyl-L-aspartate.
Archives of biochemistry and biophysics. 146(2):587-90 [PMID] 5114921.
1970
Irreversible coma associated with electrocerebral silence.
Neurology. 20(6):525-33 [PMID] 5463607.
1969
Cerebral death and the electroencephalogram. Report of the ad hoc committee of the American Electroencephalographic Society on EEG Criteria for determination of cerebral death.
JAMA. 209(10):1505-10 [PMID] 5820107.
1969
EEG and cerebral death. The neurologist’s view.
Electroencephalography and clinical neurophysiology. 27(5) [PMID] 4187060.

Grants

Jan 2014 – Oct 2015
Rescue of channelopathy induced anosmias
Role: Principal Investigator
Funding: NATL INST OF HLTH NIDCD
Apr 2013 – Mar 2019
Carbonic anhydrase and pH control in breast cancer cells
Role: Project Manager
Funding: NATL INST OF HLTH NCI

Education

Ph.D.
1968 · Columbia University
B.S.
1964 · Michigan State University

Contact Details

Phones:
Business:
(352) 256-6908
Emails:
Business:
silvrmn@ufl.edu
Addresses:
Business Mailing:
PO Box 100267
GAINESVILLE FL 32610
Business Street:
R5106 ARB
GAINESVILLE FL 32611