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PDBsum entry 1cva

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Lyase(oxo-acid) PDB id
1cva
Jmol
Contents
Protein chain
255 a.a.
Ligands
AZI
Metals
_ZN
Waters ×94

References listed in PDB file
Key reference
Title Structural and functional importance of a conserved hydrogen bond network in human carbonic anhydrase ii.
Authors J.F.Krebs, J.A.Ippolito, D.W.Christianson, C.A.Fierke.
Ref. J Biol Chem, 1993, 268, 27458-27466.
PubMed id 8262987
Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a perfect match.
Abstract
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-.
PROCHECK
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