1lgd: Difference between revisions

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[[Image:1lgd.gif|left|200px]]
{{Seed}}
[[Image:1lgd.png|left|200px]]


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{{STRUCTURE_1lgd|  PDB=1lgd  |  SCENE=  }}  
{{STRUCTURE_1lgd|  PDB=1lgd  |  SCENE=  }}  


'''Crystal Structure Analysis of HCA II Mutant T199P in Complex with Bicarbonate'''
===Crystal Structure Analysis of HCA II Mutant T199P in Complex with Bicarbonate===




==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
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{{ABSTRACT_PUBMED_12056894}}


==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]]
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