1ctt
From Proteopedia
(New page: 200px<br /><applet load="1ctt" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ctt, resolution 2.2Å" /> '''TRANSITION-STATE SELE...) |
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| - | [[Image:1ctt.gif|left|200px]]<br /><applet load="1ctt" size=" | + | [[Image:1ctt.gif|left|200px]]<br /><applet load="1ctt" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ctt, resolution 2.2Å" /> | caption="1ctt, resolution 2.2Å" /> | ||
'''TRANSITION-STATE SELECTIVITY FOR A SINGLE OH GROUP DURING CATALYSIS BY CYTIDINE DEAMINASE'''<br /> | '''TRANSITION-STATE SELECTIVITY FOR A SINGLE OH GROUP DURING CATALYSIS BY CYTIDINE DEAMINASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cytidine deaminase binds transition-state analog inhibitors approximately | + | Cytidine deaminase binds transition-state analog inhibitors approximately 10(7) times more tightly than corresponding 3,4-dihydro analogs containing a proton in place of the 4-hydroxyl group. X-ray crystal structures of complexes with the two matched inhibitors differ only near a "trapped" water molecule in the complex with the 3,4-dihydro analog, where contacts are substantially less favorable than those with the hydroxyl group of the transition-state analog. The hydrogen bond between the hydroxyl group and the Glu 104 carboxylate shortens in that complex, and may become a "low-barrier" hydrogen bond, since at the same time the bond between zinc and the Cys 132 thiolate ligand lengthens. These differences must therefore account for most of the differential binding affinity related to catalysis. Moreover, the trapped water molecule retains some of the binding energy stabilizing the hydroxyl group in the transition-state analog complex. To this extent, the ratio of binding affinities for the two compounds is smaller than the true contribution of the hydroxyl group, a conclusion with significant bearing on interpreting difference free energies derived from substituent effects arising from chemical modification and/or mutagenesis. |
==About this Structure== | ==About this Structure== | ||
| - | 1CTT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with ZN and DHZ as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cytidine_deaminase Cytidine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.5 3.5.4.5] Full crystallographic information is available from [http:// | + | 1CTT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=DHZ:'>DHZ</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cytidine_deaminase Cytidine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.5 3.5.4.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CTT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Carter, C | + | [[Category: Carter, C W.]] |
| - | [[Category: Short, S | + | [[Category: Short, S A.]] |
[[Category: Wolfenden, R.]] | [[Category: Wolfenden, R.]] | ||
[[Category: Xiang, S.]] | [[Category: Xiang, S.]] | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:09:38 2008'' |
Revision as of 10:09, 21 February 2008
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TRANSITION-STATE SELECTIVITY FOR A SINGLE OH GROUP DURING CATALYSIS BY CYTIDINE DEAMINASE
Overview
Cytidine deaminase binds transition-state analog inhibitors approximately 10(7) times more tightly than corresponding 3,4-dihydro analogs containing a proton in place of the 4-hydroxyl group. X-ray crystal structures of complexes with the two matched inhibitors differ only near a "trapped" water molecule in the complex with the 3,4-dihydro analog, where contacts are substantially less favorable than those with the hydroxyl group of the transition-state analog. The hydrogen bond between the hydroxyl group and the Glu 104 carboxylate shortens in that complex, and may become a "low-barrier" hydrogen bond, since at the same time the bond between zinc and the Cys 132 thiolate ligand lengthens. These differences must therefore account for most of the differential binding affinity related to catalysis. Moreover, the trapped water molecule retains some of the binding energy stabilizing the hydroxyl group in the transition-state analog complex. To this extent, the ratio of binding affinities for the two compounds is smaller than the true contribution of the hydroxyl group, a conclusion with significant bearing on interpreting difference free energies derived from substituent effects arising from chemical modification and/or mutagenesis.
About this Structure
1CTT is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as Cytidine deaminase, with EC number 3.5.4.5 Full crystallographic information is available from OCA.
Reference
Transition-state selectivity for a single hydroxyl group during catalysis by cytidine deaminase., Xiang S, Short SA, Wolfenden R, Carter CW Jr, Biochemistry. 1995 Apr 11;34(14):4516-23. PMID:7718553
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