1ugf
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HUMAN CARBONIC ANHYDRASE II [HCAII] (E.C.4.2.1.1) MUTANT WITH ALA 65 REPLACED BY THR (A65T)
OverviewOverview
The three-dimensional structures of A65F, A65L, A65H, A65T, A65S, and A65G, human carbonic anhydrase II (CAII) variants have been solved by X-ray, crystallographic methods to probe the importance of residue 65 and the, structural implications of its evolutionary drift in the greater family of, carbonic anhydrase isozymes. Structure-activity relationships in this, series of CAII variants are correlated with those established for other, carbonic anhydrase isozymes. We conclude that a bulky side chain at, position 65 hinders the formation of an effective solvent bridge between, zinc-bound water and H64 and thereby hinders solvent-mediated proton, transfer between these two groups [Jackman, J. E., Merz, K. M., Jr., &, Fierke, C. A. (1996) Biochemistry 35, 16421-16428]. Despite the, introduction of a polar hydroxyl group at this position, smaller side, chains such as serine or threonine substituted for A65 do not perturb the, formation of a solvent bridge between H64 and zinc-bound solvent. Thus, the evolution of residue 65 size is one factor affecting the trajectory of, catalytic proton transfer.
DiseaseDisease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this StructureAbout this Structure
1UGF is a Single protein structure of sequence from Homo sapiens with HG, ZN and AZI as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
ReferenceReference
X-ray crystallographic studies of alanine-65 variants of carbonic anhydrase II reveal the structural basis of compromised proton transfer in catalysis., Scolnick LR, Christianson DW, Biochemistry. 1996 Dec 24;35(51):16429-34. PMID:8987974
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