1j9w: Difference between revisions

Revision as of 20:57, 2 May 2008

Solution Structure of the CAI Michigan 1 Variant

OverviewOverview

The human genetic variant carbonic anhydrase I (CA I) Michigan 1 results from a single point mutation that changes His 67 to Arg in a critical region of the active site. This variant of the zinc metalloenzyme appears to be unique in that it possesses an esterase activity that is specifically enhanced by added free zinc ions. We have determined the three-dimensional structure of human CA I Michigan 1 by X-ray crystallography to a resolution of 2.6 A. In the absence of added zinc ions, the mutated residue, Arg 67, points out of the active site, hydrogen bonding with the carboxylate of Asn 69. This contrasts with the orientation of His 67, in the native isozyme, which points into the active site. The orientations of His 94, His 96, and His 119, that coordinate the catalytic zinc ion, and of the catalytically critical Thr 199-Glu 106 hydrogen bonding system, are largely unchanged in the mutant. The structure of an enzyme adduct with a second zinc bound was determined to a resolution of 2.0 A. The second zinc ion is coordinated to His 64, His 200, and Arg 67. This arginine residue reverses its orientation on zinc binding and turns into the active site. The residues at these three positions have been implicated in determining the specific kinetic properties of native CA I. This is, to our knowledge, the first example of a zinc ion coordinating with an arginine residue in a Zn(II) enzyme.

About this StructureAbout this Structure

1J9W is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of a zinc-activated variant of human carbonic anhydrase I, CA I Michigan 1: evidence for a second zinc binding site involving arginine coordination., Ferraroni M, Tilli S, Briganti F, Chegwidden WR, Supuran CT, Wiebauer KE, Tashian RE, Scozzafava A, Biochemistry. 2002 May 21;41(20):6237-44. PMID:12009884 Page seeded by OCA on Fri May 2 20:57:40 2008

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OCA

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 [[Image:1j9w.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1j9w |SIZE=350|CAPTION= <scene name='initialview01'>1j9w</scene>, resolution 2.6&Aring;
+The line below this paragraph, containing "STRUCTURE_1j9w", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1j9w|  PDB=1j9w  |  SCENE=  }}
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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1j9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j9w OCA], [http://www.ebi.ac.uk/pdbsum/1j9w PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1j9w RCSB]</span>
-}}
 '''Solution Structure of the CAI Michigan 1 Variant'''
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 [[Category: Tilli, S.]]
 [[Category: 10-stranded-beta-sheet]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 20:57:40 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:30:33 2008''