1hva

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spinqualitylabelsall models 1hva, resolution 2.3Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

ENGINEERING THE ZINC BINDING SITE OF HUMAN CARBONIC ANHYDRASE II: STRUCTURE OF THE HIS-94-> CYS APOENZYME IN A NEW CRYSTALLINE FORM

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The structure of the His-94-->Cys variant of human carbonic anhydrase II, (CAII) has been determined by X-ray crystallographic methods to a, resolution of 2.3 A with a final crystallographic R factor of 0.155. This, variant of CAII crystallizes in orthorhombic space group P2(1)2(1)2(1), which is the first example of a new crystal form for this important zinc, hydrase (the wild-type enzyme crystallizes in monoclinic space group P21, under similar crystallization conditions). Although the overall structure, of the enzyme in the orthorhombic crystal form is similar to that of the, wild-type protein in the monoclinic crystal form, the rms deviation of C, alpha atoms between the two structures is 0.5 A. Larger structural, deviations occur in regions of the protein molecule involved in crystal, lattice contacts, and significant structural changes are found in the, polypeptide strand containing Cys-94. Surprisingly, no electron density, corresponding to a zinc ion is found in the active site of crystalline, His-94-->Cys CAII, even though the stoichiometry of zinc binding to this, variant in solution is confirmed by atomic absorption spectroscopy., However, the KD for zinc dissociation from the variant is increased, 10(4)-fold compared with wild-type enzyme; furthermore, under the, crystallization conditions of high ionic strength (1.75-2.5 M ammonium, sulfate), the observed KD is increased further, which leads to zinc, dissociation. Spectroscopic analysis of Co(2+)-substituted His-94-->Cys, CAII indicates that the metal binds in a tetrahedral geometry with a new, thiolate bond.(ABSTRACT TRUNCATED AT 250 WORDS)

Disease

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

About this Structure

1HVA is a Single protein structure of sequence from Homo sapiens. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.

Reference

Engineering the zinc binding site of human carbonic anhydrase II: structure of the His-94-->Cys apoenzyme in a new crystalline form., Alexander RS, Kiefer LL, Fierke CA, Christianson DW, Biochemistry. 1993 Feb 16;32(6):1510-8. PMID:8431430

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