1lgd
From Proteopedia
(New page: 200px<br /> <applet load="1lgd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lgd, resolution 1.90Å" /> '''Crystal Structure A...) |
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| - | [[Image:1lgd.gif|left|200px]]<br /> | + | [[Image:1lgd.gif|left|200px]]<br /><applet load="1lgd" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1lgd, resolution 1.90Å" /> | caption="1lgd, resolution 1.90Å" /> | ||
'''Crystal Structure Analysis of HCA II Mutant T199P in Complex with Bicarbonate'''<br /> | '''Crystal Structure Analysis of HCA II Mutant T199P in Complex with Bicarbonate'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Substitution of Pro for Thr199 in the active site of human carbonic | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1LGD 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 and BCT as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 1LGD 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> and <scene name='pdbligand=BCT:'>BCT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1LGD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Huang, S.]] | [[Category: Huang, S.]] | ||
| - | [[Category: Jonsson, B | + | [[Category: Jonsson, B H.]] |
| - | [[Category: Sauer-Eriksson, A | + | [[Category: Sauer-Eriksson, A E.]] |
[[Category: Sjoblom, B.]] | [[Category: Sjoblom, B.]] | ||
[[Category: BCT]] | [[Category: BCT]] | ||
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[[Category: hcaii mutant t199p-bct complex]] | [[Category: hcaii mutant t199p-bct complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:44:41 2008'' |
Revision as of 11:44, 21 February 2008
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Crystal Structure Analysis of HCA II Mutant T199P in Complex with Bicarbonate
Contents |
Overview
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.
Disease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this Structure
1LGD is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
Organization of an efficient carbonic anhydrase: implications for the mechanism based on structure-function studies of a T199P/C206S mutant., Huang S, Sjoblom B, Sauer-Eriksson AE, Jonsson BH, Biochemistry. 2002 Jun 18;41(24):7628-35. PMID:12056894
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