1UGC

HUMAN CARBONIC ANHYDRASE II [HCAII] (E.C.4.2.1.1) MUTANT WITH ALA 65 REPLACED BY HIS (A65H)

Summary for 1UGC

• Entry DOI: 10.2210/pdb1ugc/pdb
• Descriptor: CARBONIC ANHYDRASE II, MERCURY (II) ION, ZINC ION, ... (4 entities in total)
• Functional Keywords: lyase, acetylation, zinc, polymorphism, disease mutation
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P00918
• Total number of polymer chains: 1
• Total formula weight: 29403.85

Authors

Scolnick, L.R.,Christianson, D.W. (deposition date: 1996-07-24, release date: 1997-04-01, Last modification date: 2024-04-03)

Primary citation

Scolnick, L.R.,Christianson, D.W.
X-ray crystallographic studies of alanine-65 variants of carbonic anhydrase II reveal the structural basis of compromised proton transfer in catalysis.
Biochemistry, 35:16429-16434, 1996

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.

PubMed: 8987974
DOI: 10.1021/bi9617872

Experimental method

X-RAY DIFFRACTION (2 Å)