1csr: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Alpha-fluoro acid and alpha-fluoro amide analogs of acetyl-coa as inhibitors of of citrate synthase: effect of pka matching on binding affinity and hydrogen bond length== | ==Alpha-fluoro acid and alpha-fluoro amide analogs of acetyl-coa as inhibitors of of citrate synthase: effect of pka matching on binding affinity and hydrogen bond length== | ||
<StructureSection load='1csr' size='340' side='right' caption='[[1csr]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='1csr' size='340' side='right' caption='[[1csr]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1csr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[1csr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CSR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CSR FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAM:ALPHA-FLUORO-AMIDOCARBOXYMETHYLDETHIA+COENZYME+A+COMPLEX'>FAM</scene>, <scene name='pdbligand=OAA:OXALOACETATE+ION'>OAA</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAM:ALPHA-FLUORO-AMIDOCARBOXYMETHYLDETHIA+COENZYME+A+COMPLEX'>FAM</scene>, <scene name='pdbligand=OAA:OXALOACETATE+ION'>OAA</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Citrate_(Si)-synthase Citrate (Si)-synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.1 2.3.3.1] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Citrate_(Si)-synthase Citrate (Si)-synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.1 2.3.3.1] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1csr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1csr OCA], [http://pdbe.org/1csr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1csr RCSB], [http://www.ebi.ac.uk/pdbsum/1csr PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1csr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1csr OCA], [http://pdbe.org/1csr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1csr RCSB], [http://www.ebi.ac.uk/pdbsum/1csr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1csr ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
| Line 26: | Line 27: | ||
</div> | </div> | ||
<div class="pdbe-citations 1csr" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1csr" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Gallus gallus]] | ||
[[Category: Remington, S J]] | [[Category: Remington, S J]] | ||
[[Category: Usher, K C]] | [[Category: Usher, K C]] | ||
[[Category: Oxo-acid-lyase]] | [[Category: Oxo-acid-lyase]] | ||
Revision as of 13:58, 8 November 2017
Alpha-fluoro acid and alpha-fluoro amide analogs of acetyl-coa as inhibitors of of citrate synthase: effect of pka matching on binding affinity and hydrogen bond lengthAlpha-fluoro acid and alpha-fluoro amide analogs of acetyl-coa as inhibitors of of citrate synthase: effect of pka matching on binding affinity and hydrogen bond length
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAn alpha-fluoro acid analog and an alpha-fluoro amide analog of acetyl-CoA have been synthesized. The ternary complexes of these inhibitors with oxaloacetate and citrate synthase have been crystallized and their structures analyzed at 1.7 A resolution. The structures are similar to those reported for the corresponding non-fluorinated analogs (Usher et al., 1994), with all forming unusually short hydrogen bonds to Asp 375. The alpha-fluoro amide analog binds with an affinity 1.5-fold lower than that of a previously described amide analog lacking the alpha-fluoro group. The alpha-fluoro acid analog binds with a 50-fold decreased affinity relative to the corresponding unfluorinated analog. The binding affinities are consistent with increased strengths of hydrogen bonds to Asp 375 with closer matching of pKa values between hydrogen bond donors and acceptors. The results do not support any direct correlation between hydrogen bond strength and hydrogen bond length in enzyme-inhibitor complexes. alpha-Fluoro acid and alpha-fluoro amide analogs of acetyl-CoA as inhibitors of citrate synthase: effect of pKa matching on binding affinity and hydrogen bond length.,Schwartz B, Drueckhammer DG, Usher KC, Remington SJ Biochemistry. 1995 Nov 28;34(47):15459-66. PMID:7492547[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References |
| ||||||||||||||||||