5ca2
From Proteopedia
(New page: 200px<br /> <applet load="5ca2" size="450" color="white" frame="true" align="right" spinBox="true" caption="5ca2, resolution 2.1Å" /> '''CONFORMATIONAL MOBIL...) |
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| - | [[Image:5ca2.gif|left|200px]]<br /> | + | [[Image:5ca2.gif|left|200px]]<br /><applet load="5ca2" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="5ca2" size=" | + | |
caption="5ca2, resolution 2.1Å" /> | caption="5ca2, resolution 2.1Å" /> | ||
'''CONFORMATIONAL MOBILITY OF HIS-64 IN THE THR-200 (RIGHT ARROW) SER MUTANT OF HUMAN CARBONIC ANHYDRASE II'''<br /> | '''CONFORMATIONAL MOBILITY OF HIS-64 IN THE THR-200 (RIGHT ARROW) SER MUTANT OF HUMAN CARBONIC ANHYDRASE II'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The three-dimensional structure of the Thr-200----Ser (T200S) mutant of | + | The three-dimensional structure of the Thr-200----Ser (T200S) mutant of human carbonic anhydrase II (CAII) has been determined by X-ray crystallographic methods at 2.1-A resolution. This particular mutant of CAII exhibits CO2 hydrase activity that is comparable to that of the wild-type enzyme with a 2-fold stabilization of the E.HCO3- complex and esterase activity that is 4-fold greater than that of the wild-type enzyme. The structure of the mutant enzyme reveals no significant local changes accompanying the conservative T200S substitution, but an important nonlocal structural change is evident: the side chain of catalytic residue His-64 rotates away from the active site by 105 degrees about chi 1 and apparently displaces a water molecule. The displaced water molecule is present in the wild-type enzyme; however, the electron density into which this water is built is interpretable as an alternate conformation of His-64 with 10-20% occupancy. The rate constants for proton transfer from the zinc-water ligand to His-64 and from His-64 to bulk solvent are maintained in the T200S variant; therefore, if His-64 is conformationally mobile about chi 1 and/or chi 2 during catalysis, compensatory changes in solvent configuration must sustain efficient proton transfer. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 5CA2 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 HG 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:// | + | 5CA2 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=HG:'>HG</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=5CA2 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Alexander, R | + | [[Category: Alexander, R S.]] |
| - | [[Category: Christianson, D | + | [[Category: Christianson, D W.]] |
[[Category: HG]] | [[Category: HG]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: lyase(oxo-acid)]] | [[Category: lyase(oxo-acid)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:14:57 2008'' |
Revision as of 17:15, 21 February 2008
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CONFORMATIONAL MOBILITY OF HIS-64 IN THE THR-200 (RIGHT ARROW) SER MUTANT OF HUMAN CARBONIC ANHYDRASE II
Contents |
Overview
The three-dimensional structure of the Thr-200----Ser (T200S) mutant of human carbonic anhydrase II (CAII) has been determined by X-ray crystallographic methods at 2.1-A resolution. This particular mutant of CAII exhibits CO2 hydrase activity that is comparable to that of the wild-type enzyme with a 2-fold stabilization of the E.HCO3- complex and esterase activity that is 4-fold greater than that of the wild-type enzyme. The structure of the mutant enzyme reveals no significant local changes accompanying the conservative T200S substitution, but an important nonlocal structural change is evident: the side chain of catalytic residue His-64 rotates away from the active site by 105 degrees about chi 1 and apparently displaces a water molecule. The displaced water molecule is present in the wild-type enzyme; however, the electron density into which this water is built is interpretable as an alternate conformation of His-64 with 10-20% occupancy. The rate constants for proton transfer from the zinc-water ligand to His-64 and from His-64 to bulk solvent are maintained in the T200S variant; therefore, if His-64 is conformationally mobile about chi 1 and/or chi 2 during catalysis, compensatory changes in solvent configuration must sustain efficient proton transfer.
Disease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this Structure
5CA2 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
Conformational mobility of His-64 in the Thr-200----Ser mutant of human carbonic anhydrase II., Krebs JF, Fierke CA, Alexander RS, Christianson DW, Biochemistry. 1991 Sep 24;30(38):9153-60. PMID:1909891
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