4ca2
From Proteopedia
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ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE II
Contents |
Overview
Wild-type and mutant human carbonic anhydrases II, where mutations have, been made in the hydrophobic pocket of the active site, have been studied, by X-ray crystallographic methods. Specifically, mutations at Val-143 (the, base of the pocket) lead to significant changes in catalytic activity and, protein structure. The obliteration of a well-defined pocket in the, Val-143----Phe and Val-143----Tyr mutants results in significantly, diminished enzyme activity [(5 x 10(4))-fold and (3 x 10(5))-fold, respectively]; however, the activity of the Val-143----His mutant is, diminished less (10(2)-fold), and deepening the pocket in the, Val-143----Gly mutant results in only a 2-fold decrease in activity, [Fierke et al., 1991 (preceding paper in this issue)]. These results, indicate that the hydrophobic pocket is important for substrate, association with the enzyme, but there are probably several catalytically, acceptable substrate trajectories through this region of the enzyme, structure. Additionally, each mutant protein exhibits long-range (ca., 10-15 A) compensatory structural changes which accommodate the Val-143, substitution. As such, the genetic-structural approach represented in this, work serves as a three-dimensional paradigm for the redesign of, specificity pockets in other protein catalysts.
Disease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this Structure
4CA2 is a Single protein structure of sequence from Homo sapiens with ZN and HG as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
Engineering the hydrophobic pocket of carbonic anhydrase II., Alexander RS, Nair SK, Christianson DW, Biochemistry. 1991 Nov 19;30(46):11064-72. PMID:1932029
Page seeded by OCA on Mon Nov 12 23:50:20 2007
