1ugg
HUMAN CARBONIC ANHYDRASE II[HCAII] (E.C.4.2.1.1) MUTANT WITH ALA 65 REPLACED BY SER (A65S)-ORTHORHOMBIC FORM
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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
1UGG is a Single protein structure of sequence from Homo sapiens with as ligand. 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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