1cvd
From Proteopedia
(New page: 200px<br /> <applet load="1cvd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cvd, resolution 2.2Å" /> '''STRUCTURAL CONSEQUEN...) |
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caption="1cvd, resolution 2.2Å" /> | caption="1cvd, resolution 2.2Å" /> | ||
'''STRUCTURAL CONSEQUENCES OF REDESIGNING A PROTEIN-ZINC BINDING SITE'''<br /> | '''STRUCTURAL CONSEQUENCES OF REDESIGNING A PROTEIN-ZINC BINDING SITE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1CVD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] Full crystallographic information is available from [http:// | + | 1CVD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CVD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: lyase(oxo-acid)]] | [[Category: lyase(oxo-acid)]] | ||
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Revision as of 13:37, 15 February 2008
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STRUCTURAL CONSEQUENCES OF REDESIGNING A PROTEIN-ZINC BINDING SITE
Contents |
Overview
In order to probe the structural importance of zinc ligands in the active, site of human carbonic anhydrase II (CAII), we have determined the, three-dimensional structures of H94C (in metal-bound form), H94C-BME, (i.e., disulfide-linked with beta-mercaptoethanol), H94A, H96C, H119C, and, H119D variants of CAII by X-ray crystallographic methods at resolutions of, 2.2, 2.35, 2.25, 2.3, 2.2, and 2.25 A, respectively. Each variant, crystallizes isomorphously with the wild-type enzyme, in which zinc is, tetrahedrally coordinated by H94, H96, H119, and hydroxide ion. The, structure of H94C CAII reveals the successful substitution of the, naturally occurring histidine zinc ligand by a cysteine thiolate, and, metal coordination by C94 is facilitated by the plastic structural, response of the beta-sheet superstructure. Importantly, the resulting, structure represents the catalytically active form of the enzyme reported, previously [Alexander, R. S., Kiefer, L. L., Fierke, C. A., &, Christianson, D. W. (1993) Biochemistry 32, 1510-1518]. Contrastingly, the, structure of H96C CAII reveals that the engineered side chain does not, coordinate to zinc; instead, zinc is tetrahedrally liganded by H94, H119, and two solvent molecules. Thus, the beta-sheet superstructure is not, sufficiently plastic in this location to allow C96 to coordinate to the, metal ion. Substitution of the thiolate or carboxylate group for wild-type, histidine in H119C and H119D CAIIs reveals that tetrahedral metal, coordination is maintained in each variant; however, since there is no, plastic structural response of the corresponding beta-strand, a longer, metal-ligand separation results.(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
1CVD is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
Structural consequences of redesigning a protein-zinc binding site., Ippolito JA, Christianson DW, Biochemistry. 1994 Dec 27;33(51):15241-9. PMID:7803386
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