1a42

From Proteopedia

Revision as of 11:58, 18 December 2007

HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH BRINZOLAMIDE

Overview

Carbonic anhydrase IV (CAIV) is a membrane-associated enzyme anchored to, plasma membrane surfaces by a phosphatidylinositol glycan linkage. We have, determined the 2.8-angstroms resolution crystal structure of a truncated, soluble form of recombinant murine CAIV. We have also determined the, structure of its complex with a drug used for glaucoma therapy, the, sulfonamide inhibitor brinzolamide (Azopt). The overall structure of, murine CAIV is generally similar to that of human CAIV; however, some, local structural differences are found in the active site resulting from, amino acid sequence differences in the "130's segment" and the residue-63, loop (these may affect the nearby catalytic proton shuttle, His-64)., Similar to human CAIV, the C-terminus of murine CAIV is surrounded by a, substantial electropositive surface potential that may stabilize the, interaction with the phospholipid membrane. Binding interactions observed, for brinzolamide rationalize the generally weaker affinity of inhibitors, used in glaucoma therapy toward CAIV compared with CAII.

Disease

Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]

About this Structure

1A42 is a Single protein structure of sequence from Homo sapiens with HG, ZN and BZU as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: molecular basis of isozyme-drug discrimination., Stams T, Chen Y, Boriack-Sjodin PA, Hurt JD, Liao J, May JA, Dean T, Laipis P, Silverman DN, Christianson DW, Protein Sci. 1998 Mar;7(3):556-63. PMID:9541386

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