1z12: Difference between revisions
New page: left|200px<br /><applet load="1z12" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z12, resolution 2.2Å" /> '''Crystal Structure of ... |
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[[Image:1z12.gif|left|200px]]<br /><applet load="1z12" size=" | [[Image:1z12.gif|left|200px]]<br /><applet load="1z12" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1z12, resolution 2.2Å" /> | caption="1z12, resolution 2.2Å" /> | ||
'''Crystal Structure of Bovine Low Molecular Weight PTPase Complexed with Vanadate'''<br /> | '''Crystal Structure of Bovine Low Molecular Weight PTPase Complexed with Vanadate'''<br /> | ||
==Overview== | ==Overview== | ||
The early transition metal oxoanions vanadate, molybdate, and tungstate | The early transition metal oxoanions vanadate, molybdate, and tungstate are widely used inhibitors for phosphatase enzymes. These oxoanions could inhibit such enzymes by simply mimicking the tetrahedral geometry of phosphate ion. However, in some cases, the enzyme-inhibitor dissociation constants (Ki) for these oxoanions are much lower than that for phosphate. Such observations gave rise to the hypothesis that in some cases these transition metal oxoanions may inhibit phosphomonoesterases by forming complexes that resemble the trigonal bipyramidal geometry of the SN2(P) transition state. As a test of this, the crystal structures of a low molecular weight protein tyrosine phosphatase at pH 7.5 complexed with the inhibitors vanadate and molybdate were solved at 2.2 A resolution and compared to a newly refined 1.9 A structure of the enzyme. Geometric restraints on the oxoanions were relaxed during refinement in order to minimize model bias. Both inhibitors were bound at the active site, and the overall protein structures were left unchanged, although some small but significant side chain movements at the active site were observed. Vanadate ion formed a covalent linkage with the nucleophile Cys12 at the active site and exhibited a trigonal bipyramidal geometry. In contrast, simple tetrahedral geometry was observed for the weaker molybdate complex. These studies are consistent with the conclusion that vanadate inhibits tyrosine phosphatases by acting as a transition state analog. The structure of the vanadate complex may be expected to closely resemble the transition state for reactions catalyzed by protein tyrosine phosphatases. | ||
==About this Structure== | ==About this Structure== | ||
1Z12 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with VO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1Z12 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=VO4:'>VO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z12 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Etten, R | [[Category: Etten, R L.Van.]] | ||
[[Category: Stauffacher, C | [[Category: Stauffacher, C V.]] | ||
[[Category: Zhang, M.]] | [[Category: Zhang, M.]] | ||
[[Category: Zhou, M.]] | [[Category: Zhou, M.]] | ||
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[[Category: vanadate complex]] | [[Category: vanadate complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:11:07 2008'' | ||
Revision as of 17:11, 21 February 2008
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Crystal Structure of Bovine Low Molecular Weight PTPase Complexed with Vanadate
OverviewOverview
The early transition metal oxoanions vanadate, molybdate, and tungstate are widely used inhibitors for phosphatase enzymes. These oxoanions could inhibit such enzymes by simply mimicking the tetrahedral geometry of phosphate ion. However, in some cases, the enzyme-inhibitor dissociation constants (Ki) for these oxoanions are much lower than that for phosphate. Such observations gave rise to the hypothesis that in some cases these transition metal oxoanions may inhibit phosphomonoesterases by forming complexes that resemble the trigonal bipyramidal geometry of the SN2(P) transition state. As a test of this, the crystal structures of a low molecular weight protein tyrosine phosphatase at pH 7.5 complexed with the inhibitors vanadate and molybdate were solved at 2.2 A resolution and compared to a newly refined 1.9 A structure of the enzyme. Geometric restraints on the oxoanions were relaxed during refinement in order to minimize model bias. Both inhibitors were bound at the active site, and the overall protein structures were left unchanged, although some small but significant side chain movements at the active site were observed. Vanadate ion formed a covalent linkage with the nucleophile Cys12 at the active site and exhibited a trigonal bipyramidal geometry. In contrast, simple tetrahedral geometry was observed for the weaker molybdate complex. These studies are consistent with the conclusion that vanadate inhibits tyrosine phosphatases by acting as a transition state analog. The structure of the vanadate complex may be expected to closely resemble the transition state for reactions catalyzed by protein tyrosine phosphatases.
About this StructureAbout this Structure
1Z12 is a Single protein structure of sequence from Bos taurus with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of bovine low molecular weight phosphotyrosyl phosphatase complexed with the transition state analog vanadate., Zhang M, Zhou M, Van Etten RL, Stauffacher CV, Biochemistry. 1997 Jan 7;36(1):15-23. PMID:8993313
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