3ioc
From Proteopedia
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| - | + | ==Crystal Structure of Mycobacterium Tuberculosis Pantothenate Synthetase at 2.50 Ang resolution in complex with 5'-deoxy-5'-(benzyldisulfanyl)-adenosine== | |
| - | + | <StructureSection load='3ioc' size='340' side='right' caption='[[3ioc]], [[Resolution|resolution]] 2.50Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[3ioc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IOC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3IOC FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A5D:(2R,3R,4S,5S)-2-(6-AMINO-9H-PURIN-9-YL)-5-[(BENZYLDISULFANYL)METHYL]TETRAHYDROFURAN-3,4-DIOL'>A5D</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3cov|3cov]], [[3cow|3cow]], [[3coy|3coy]], [[3coz|3coz]], [[1n2h|1n2h]], [[3iob|3iob]], [[3iod|3iod]], [[3ioe|3ioe]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MT3707, MTCY07H7B.20, panC, Rv3602c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pantoate--beta-alanine_ligase Pantoate--beta-alanine ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.1 6.3.2.1] </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=3ioc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ioc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ioc RCSB], [http://www.ebi.ac.uk/pdbsum/3ioc PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/io/3ioc_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A new strategy that combines the concepts of fragment-based drug design and dynamic combinatorial chemistry (DCC) for targeting adenosine recognition sites on enzymes is reported. We demonstrate the use of 5'-deoxy-5'-thioadenosine as a noncovalent anchor fragment in dynamic combinatorial libraries templated by Mycobacterium tuberculosis pantothenate synthetase. A benzyl disulfide derivative was identified upon library analysis by HPLC. Structural and binding studies of protein-ligand complexes by X-ray crystallography and isothermal titration calorimetry informed the subsequent optimisation of the DCC hit into a disulfide containing the novel meta-nitrobenzyl fragment that targets the pantoate binding site of pantothenate synthetase. Given the prevalence of adenosine-recognition motifs in enzymes, our results provide a proof-of-concept for using this strategy to probe adjacent pockets for a range of adenosine binding enzymes, including other related adenylate-forming ligases, kinases, and ATPases, as well as NAD(P)(H), CoA and FAD(H2) binding proteins. | ||
| - | + | A fragment-based approach to probing adenosine recognition sites by using dynamic combinatorial chemistry.,Scott DE, Dawes GJ, Ando M, Abell C, Ciulli A Chembiochem. 2009 Nov 23;10(17):2772-9. PMID:19827080<ref>PMID:19827080</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
==See Also== | ==See Also== | ||
*[[Pantothenate synthetase|Pantothenate synthetase]] | *[[Pantothenate synthetase|Pantothenate synthetase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Pantoate--beta-alanine ligase]] | [[Category: Pantoate--beta-alanine ligase]] | ||
| - | [[Category: Abell, C | + | [[Category: Abell, C]] |
| - | [[Category: Ciulli, A | + | [[Category: Ciulli, A]] |
| - | [[Category: Scott, D E | + | [[Category: Scott, D E]] |
[[Category: Atp-binding]] | [[Category: Atp-binding]] | ||
[[Category: Drug design]] | [[Category: Drug design]] | ||
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[[Category: Magnesium]] | [[Category: Magnesium]] | ||
[[Category: Metal-binding]] | [[Category: Metal-binding]] | ||
| - | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Nucleotide-binding]] | [[Category: Nucleotide-binding]] | ||
[[Category: Pantothenate biosynthesis]] | [[Category: Pantothenate biosynthesis]] | ||
Revision as of 16:51, 18 December 2014
Crystal Structure of Mycobacterium Tuberculosis Pantothenate Synthetase at 2.50 Ang resolution in complex with 5'-deoxy-5'-(benzyldisulfanyl)-adenosine
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