5ca2

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spinqualitylabelsall models 5ca2, resolution 2.1Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CONFORMATIONAL MOBILITY OF HIS-64 IN THE THR-200 (RIGHT ARROW) SER MUTANT OF HUMAN CARBONIC ANHYDRASE II

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The three-dimensional structure of the Thr-200----Ser (T200S) mutant of, human carbonic anhydrase II (CAII) has been determined by X-ray, crystallographic methods at 2.1-A resolution. This particular mutant of, CAII exhibits CO2 hydrase activity that is comparable to that of the, wild-type enzyme with a 2-fold stabilization of the E.HCO3- complex and, esterase activity that is 4-fold greater than that of the wild-type, enzyme. The structure of the mutant enzyme reveals no significant local, changes accompanying the conservative T200S substitution, but an important, nonlocal structural change is evident: the side chain of catalytic residue, His-64 rotates away from the active site by 105 degrees about chi 1 and, apparently displaces a water molecule. The displaced water molecule is, present in the wild-type enzyme; however, the electron density into which, this water is built is interpretable as an alternate conformation of, His-64 with 10-20% occupancy. The rate constants for proton transfer from, the zinc-water ligand to His-64 and from His-64 to bulk solvent are, maintained in the T200S variant; therefore, if His-64 is conformationally, mobile about chi 1 and/or chi 2 during catalysis, compensatory changes in, solvent configuration must sustain efficient proton transfer.

Disease

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

About this Structure

5CA2 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

Conformational mobility of His-64 in the Thr-200----Ser mutant of human carbonic anhydrase II., Krebs JF, Fierke CA, Alexander RS, Christianson DW, Biochemistry. 1991 Sep 24;30(38):9153-60. PMID:1909891

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