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|1z97, resolution 2.10Å ()|
|Gene:||CA3 (Homo sapiens)|
Human Carbonic Anhydrase III: Structural and Kinetic Study of Catalysis and Proton Transfer.
The residue phenylalanine 198 (Phe 198) is a prominent cause of the lower activity of human carbonic anhydrase III (HCA III) compared with HCA II and other isozymes which have leucine at this site. We report the crystal structures of HCA III and the site-directed mutant F198L HCA III, both at 2.1 A resolution, and the enhancement of catalytic activity by exogenous proton donors containing imidazole rings. Both enzymes had a hexahistidine extension at the carboxy-terminal end, used to aid in purification, that was ordered in the crystal structures bound in the active site cavity of an adjacent symmetry-related enzyme. This observation allowed us to comment on a number of possible binding sites for imidazole and derivatives as exogenous proton donors/acceptors in catalysis by HCA III. Kinetic and structural evidence indicates that the phenyl side chain of Phe 198 in HCA III, about 5 A from the zinc, is a steric constriction in the active site, may cause altered interactions at the zinc-bound solvent, and is a binding site for the activation of catalysis by histidylhistidine. This suggests that sites of activation of the proton-transfer pathway in carbonic anhydrase are closer to the zinc than considered in previous studies.
Human carbonic anhydrase III: structural and kinetic study of catalysis and proton transfer., Duda DM, Tu C, Fisher SZ, An H, Yoshioka C, Govindasamy L, Laipis PJ, Agbandje-McKenna M, Silverman DN, McKenna R, Biochemistry. 2005 Aug 2;44(30):10046-53. PMID:16042381
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Duda DM, Tu C, Fisher SZ, An H, Yoshioka C, Govindasamy L, Laipis PJ, Agbandje-McKenna M, Silverman DN, McKenna R. Human carbonic anhydrase III: structural and kinetic study of catalysis and proton transfer. Biochemistry. 2005 Aug 2;44(30):10046-53. PMID:16042381 doi:http://dx.doi.org/10.1021/bi050610h