12ca

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spinqualitylabelsall models 12ca, resolution 2.4Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

ALTERING THE MOUTH OF A HYDROPHOBIC POCKET. STRUCTURE AND KINETICS OF HUMAN CARBONIC ANHYDRASE II MUTANTS AT RESIDUE VAL-121

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Eleven amino acid substitutions at Val-121 of human carbonic anhydrase II, including Gly, Ala, Ser, Leu, Ile, Lys, and Arg, were constructed by, site-directed mutagenesis. This residue is at the mouth of the hydrophobic, pocket in the enzyme active site. The CO2 hydrase activity and the, p-nitrophenyl esterase activity of these CAII variants correlate with the, hydrophobicity of the residue, suggesting that the hydrophobic character, of this residue is important for catalysis. The effects of these mutations, on the steady-state kinetics for CO2 hydration occur mainly in kcat/Km and, Km, consistent with involvement of this residue in CO2 association. The, Val-121----Ala mutant, which exhibits about one-third normal CO2 hydrase, activity, has been studied by x-ray crystallographic methods. No, significant changes in the mutant enzyme conformation are evident relative, to the wild-type enzyme. Since Val-121 is at the mouth of the hydrophobic, pocket, its substitution by the methyl side chain of alanine makes the, pocket mouth significantly wider than that of the wild-type enzyme. Hence, although a moderately wide (and deep) pocket is important for substrate, association, a wider mouth to this pocket does not seriously compromise, the catalytic approach of CO2 toward nucleophilic zinc-bound hydroxide.

Disease

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

About this Structure

12CA 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

Altering the mouth of a hydrophobic pocket. Structure and kinetics of human carbonic anhydrase II mutants at residue Val-121., Nair SK, Calderone TL, Christianson DW, Fierke CA, J Biol Chem. 1991 Sep 15;266(26):17320-5. PMID:1910042

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