1h9q: Difference between revisions
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'''H119Q CARBONIC ANHYDRASE II''' | '''H119Q CARBONIC ANHYDRASE II''' | ||
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[[Category: Christianson, D W.]] | [[Category: Christianson, D W.]] | ||
[[Category: Lesburg, C A.]] | [[Category: Lesburg, C A.]] | ||
[[Category: | [[Category: Acetylation]] | ||
[[Category: | [[Category: Lyase]] | ||
[[Category: | [[Category: Oxo-acid]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:36:48 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 18:36, 2 May 2008
H119Q CARBONIC ANHYDRASE II
OverviewOverview
The catalytic zinc ion of human carbonic anhydrase II (CAII) is coordinated by three histidine ligands (H94, H96, and H119) and a hydroxide ion with tetrahedral geometry. Structural and functional analysis of variants in which the zinc ligands H94 and H119 are substituted with asparagine and glutamine, and comparison with results obtained with aspartate and glutamate substitutions indicate that the neutral ligand field provided by the protein optimizes the electrostatic environment for the catalytic function of the metal ion, including stabilization of bound anions. This is demonstrated by catalytic activity measurements for ester hydrolysis and CO2 hydration, as well as sulfonamide inhibitor affinity assays. High-resolution X-ray crystal structure determinations of H94N, H119N, and H119Q CAIIs reveal that the engineered carboxamide side chains coordinate to zinc with optimal stereochemistry. However, zinc coordination geometry remains tetrahedral only in H119Q CAII. Metal geometry changes to trigonal bipyramidal in H119N CAII due to the addition of a second water molecule to the zinc coordination polyhedron and also in H94N CAII due to the displacement of zinc-bound hydroxide by the bidentate coordination of a Tris molecule. Possibly, the bulky histidine imidazole ligands of the native enzyme play a role in disfavoring trigonal bipyramidal coordination geometry for zinc. Protein-metal affinity is significantly compromised by all histidine --> carboxamide ligand substitutions. Diminished affinity may result from significant movements (up to 1 A) of the metal ion from its position in the wild-type enzyme, as well as the associated, minor conformational changes of metal ligands and their neighboring residues.
About this StructureAbout this Structure
1H9Q is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Histidine --> carboxamide ligand substitutions in the zinc binding site of carbonic anhydrase II alter metal coordination geometry but retain catalytic activity., Lesburg CA, Huang C, Christianson DW, Fierke CA, Biochemistry. 1997 Dec 16;36(50):15780-91. PMID:9398308 Page seeded by OCA on Fri May 2 18:36:48 2008