X-ray crystallographic studies of alanine-65 variants of carbonic anhydrase II reveal the structural basis of compromised proton transfer in catalysis.

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Scolnick LR, Christianson DW

X-ray crystallographic studies of alanine-65 variants of carbonic anhydrase II reveal the structural basis of compromised proton transfer in catalysis.

Biochemistry. 1996 Dec 24;35(51):16429-34.

PubMed ID
8987974 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Carbonic anhydrase 2P00918Details