1cvb: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 1cvb |SIZE=350|CAPTION= <scene name='initialview01'>1cvb</scene>, resolution 2.4Å | |PDB= 1cvb |SIZE=350|CAPTION= <scene name='initialview01'>1cvb</scene>, resolution 2.4Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1cvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cvb OCA], [http://www.ebi.ac.uk/pdbsum/1cvb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1cvb RCSB]</span> | |||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
Amino acid substitutions at Thr199 of human carbonic anhydrase II (CAII) (Thr199-->Ser, Ala, Val, and Pro) were characterized to investigate the importance of a conserved hydrogen bonding network. The three-dimensional structures of azide-bound and sulfate-bound T199V CAIIs were determined by x-ray crystallographic methods at 2.25 and 2.4 A, respectively (final crystallographic R factors are 0.173 and 0.174, respectively). The CO2 hydrase activities of T199S and T199P variants suggest that the side chain methyl and backbone amino functionalities stabilize the transition state by approximately 0.4 and 0.8 kcal/mol, respectively. The side chain hydroxyl group causes: stabilization of zinc-hydroxide relative to zinc-water (pKa increases approximately 2 units); stabilization of the transition state for bicarbonate dehydration relative to the CAII.HCO3- complex (approximately 5 kcal/mol); and destabilization of the CAII.HCO3- complex (approximately 0.8 kcal/mol). An inverse correlation between log(kcatCO2/KM) and the pKa of zinc-water (r = 0.95, slope = -1) indicates that the hydrogen bonding network stabilizes the chemical transition state and zinc-hydroxide similarly. These data are consistent with the hydroxyl group of Thr199 forming a hydrogen bond with the transition state and a non-hydrogen-bonded van der Waals contact with CAII.HCO3-. | Amino acid substitutions at Thr199 of human carbonic anhydrase II (CAII) (Thr199-->Ser, Ala, Val, and Pro) were characterized to investigate the importance of a conserved hydrogen bonding network. The three-dimensional structures of azide-bound and sulfate-bound T199V CAIIs were determined by x-ray crystallographic methods at 2.25 and 2.4 A, respectively (final crystallographic R factors are 0.173 and 0.174, respectively). The CO2 hydrase activities of T199S and T199P variants suggest that the side chain methyl and backbone amino functionalities stabilize the transition state by approximately 0.4 and 0.8 kcal/mol, respectively. The side chain hydroxyl group causes: stabilization of zinc-hydroxide relative to zinc-water (pKa increases approximately 2 units); stabilization of the transition state for bicarbonate dehydration relative to the CAII.HCO3- complex (approximately 5 kcal/mol); and destabilization of the CAII.HCO3- complex (approximately 0.8 kcal/mol). An inverse correlation between log(kcatCO2/KM) and the pKa of zinc-water (r = 0.95, slope = -1) indicates that the hydrogen bonding network stabilizes the chemical transition state and zinc-hydroxide similarly. These data are consistent with the hydroxyl group of Thr199 forming a hydrogen bond with the transition state and a non-hydrogen-bonded van der Waals contact with CAII.HCO3-. | ||
==About this Structure== | ==About this Structure== | ||
| Line 28: | Line 28: | ||
[[Category: Christianson, D W.]] | [[Category: Christianson, D W.]] | ||
[[Category: Ippolito, J A.]] | [[Category: Ippolito, J A.]] | ||
[[Category: lyase(oxo-acid)]] | [[Category: lyase(oxo-acid)]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:29:20 2008'' | ||
Revision as of 19:29, 30 March 2008
| |||||||
| , resolution 2.4Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Carbonate dehydratase, with EC number 4.2.1.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURAL AND FUNCTIONAL IMPORTANCE OF A CONSERVED HYDROGEN BOND NETWORK IN HUMAN CARBONIC ANHYDRASE II
OverviewOverview
Amino acid substitutions at Thr199 of human carbonic anhydrase II (CAII) (Thr199-->Ser, Ala, Val, and Pro) were characterized to investigate the importance of a conserved hydrogen bonding network. The three-dimensional structures of azide-bound and sulfate-bound T199V CAIIs were determined by x-ray crystallographic methods at 2.25 and 2.4 A, respectively (final crystallographic R factors are 0.173 and 0.174, respectively). The CO2 hydrase activities of T199S and T199P variants suggest that the side chain methyl and backbone amino functionalities stabilize the transition state by approximately 0.4 and 0.8 kcal/mol, respectively. The side chain hydroxyl group causes: stabilization of zinc-hydroxide relative to zinc-water (pKa increases approximately 2 units); stabilization of the transition state for bicarbonate dehydration relative to the CAII.HCO3- complex (approximately 5 kcal/mol); and destabilization of the CAII.HCO3- complex (approximately 0.8 kcal/mol). An inverse correlation between log(kcatCO2/KM) and the pKa of zinc-water (r = 0.95, slope = -1) indicates that the hydrogen bonding network stabilizes the chemical transition state and zinc-hydroxide similarly. These data are consistent with the hydroxyl group of Thr199 forming a hydrogen bond with the transition state and a non-hydrogen-bonded van der Waals contact with CAII.HCO3-.
About this StructureAbout this Structure
1CVB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural and functional importance of a conserved hydrogen bond network in human carbonic anhydrase II., Krebs JF, Ippolito JA, Christianson DW, Fierke CA, J Biol Chem. 1993 Dec 25;268(36):27458-66. PMID:8262987
Page seeded by OCA on Sun Mar 30 19:29:20 2008