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| [[Image:1lgd.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1lgd| PDB=1lgd | SCENE= }} | | {{STRUCTURE_1lgd| PDB=1lgd | SCENE= }} |
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| '''Crystal Structure Analysis of HCA II Mutant T199P in Complex with Bicarbonate'''
| | ===Crystal Structure Analysis of HCA II Mutant T199P in Complex with Bicarbonate=== |
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| ==Overview==
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| Substitution of Pro for Thr199 in the active site of human carbonic anhydrase II (HCA II)(1) reduces its catalytic efficiency about 3000-fold. X-ray crystallographic structures of the T199P/C206S variant have been determined in complex with the substrate bicarbonate and with the inhibitors thiocyanate and beta-mercaptoethanol. The latter molecule is normally not an inhibitor of wild-type HCA II. All three ligands display novel binding interactions to the T199P/C206S mutant. The beta-mercaptoethanol molecule binds in the active site area with its sulfur atom tetrahedrally coordinated to the zinc ion. Thiocyanate binds tetrahedrally coordinated to the zinc ion in T199P/C206S, in contrast to its pentacoordinated binding to the zinc ion in wild-type HCA II. Bicarbonate binds to the mutant with two of its oxygens at the positions of the zinc water (Wat263) and Wat318 in wild-type HCA II. The environment of this area is more hydrophilic than the normal bicarbonate-binding site of HCA II situated in the hydrophobic part of the cavity normally occupied by the so-called deep water (Wat338). The observation of a new binding site for bicarbonate has implications for understanding the mechanism by which the main-chain amino group of Thr199 acquired an important role for orientation of the substrate during the evolution of the enzyme.
| | The line below this paragraph, {{ABSTRACT_PUBMED_12056894}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 12056894 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_12056894}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Sjoblom, B.]] | | [[Category: Sjoblom, B.]] |
| [[Category: Hcaii mutant t199p-bct complex]] | | [[Category: Hcaii mutant t199p-bct complex]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:53:43 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 20:52:28 2008'' |