3iod: Difference between revisions
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==Crystal Structure of Mycobacterium Tuberculosis Pantothenate Synthetase at 1.75 Ang resolution in complex with 5'-deoxy-5'-((3-nitrobenzyl)disulfanyl)-adenosine== | |||
<StructureSection load='3iod' size='340' side='right' caption='[[3iod]], [[Resolution|resolution]] 1.75Å' scene=''> | |||
{ | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3iod]] 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=3IOD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3IOD FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A6D:(2R,3R,4S,5S)-2-(6-AMINO-9H-PURIN-9-YL)-5-{[(3-NITROBENZYL)DISULFANYL]METHYL}TETRAHYDROFURAN-3,4-DIOL'>A6D</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]], [[3iob|3iob]], [[3ioc|3ioc]], [[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=3iod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iod OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3iod RCSB], [http://www.ebi.ac.uk/pdbsum/3iod 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/3iod_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: Nucleotide-binding]] | [[Category: Nucleotide-binding]] | ||
[[Category: Pantothenate biosynthesis]] | [[Category: Pantothenate biosynthesis]] | ||
Revision as of 18:14, 18 December 2014
Crystal Structure of Mycobacterium Tuberculosis Pantothenate Synthetase at 1.75 Ang resolution in complex with 5'-deoxy-5'-((3-nitrobenzyl)disulfanyl)-adenosineCrystal Structure of Mycobacterium Tuberculosis Pantothenate Synthetase at 1.75 Ang resolution in complex with 5'-deoxy-5'-((3-nitrobenzyl)disulfanyl)-adenosine
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 PubMedA 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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