3twp: Difference between revisions

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-{{STRUCTURE_3twp|  PDB=3twp  |  SCENE=  }}
+==Crystal structure of M. tuberculosis TrpD in complex with an inhibitor==
-===Crystal structure of M. tuberculosis TrpD in complex with an inhibitor===
+<StructureSection load='3twp' size='340' side='right' caption='[[3twp]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
-{{ABSTRACT_PUBMED_23363292}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3twp]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TWP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TWP FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PRP:ALPHA-PHOSPHORIBOSYLPYROPHOSPHORIC+ACID'>PRP</scene>, <scene name='pdbligand=SAL:2-HYDROXYBENZOIC+ACID'>SAL</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qr9|3qr9]], [[3qqs|3qqs]], [[3qs8|3qs8]], [[3r6c|3r6c]], [[3qsa|3qsa]], [[3r88|3r88]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MT2248, MTCY190.03c, Rv2192c, trpD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Anthranilate_phosphoribosyltransferase Anthranilate phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.18 2.4.2.18] </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=3twp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3twp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3twp RCSB], [http://www.ebi.ac.uk/pdbsum/3twp PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Anthranilate phosphoribosyltransferase (AnPRT, EC 2.4.2.18) is a homodimeric enzyme that catalyzes the reaction between 5'-phosphoribosyl-1'-pyrophosphate (PRPP) and anthranilate, as part of the tryptophan biosynthesis pathway. Here we present the results of the first chemical screen for inhibitors against Mycobacterium tuberculosis (Mtb) AnPRT, along with crystal structures of Mtb-AnPRT in complex with PRPP and several inhibitors. Previous work revealed that PRPP is bound at the base of a deep cleft in Mtb-AnPRT, and predicted two anthranilate binding sites along the tunnel leading to the PRPP binding site. Unexpectedly, the inhibitors presented here almost exclusively bound at the entrance of the tunnel, in the presumed non-catalytic anthranilate binding site, previously hypothesized to have a role in substrate capture. The potencies of the inhibitors were measured, yielding Ki values from 1.5 - 119 muM, with the strongest inhibition displayed by a bi-anthranilate compound that makes hydrogen bond and salt bridge contacts with Mtb-AnPRT via its carboxyl groups. Our results reveal how the substrate capture mechanism of AnPRT can be exploited to inhibit the enzyme's activity and provide a scaffold for the design of improved Mtb-AnPRT inhibitors that may ultimately form the basis of new anti-tuberculosis drugs with a novel mode of action.
-==About this Structure==
+Substrate capture mechanism of Mycobacterium tuberculosis anthranilate phosphoribosyltransferase provides a mode for inhibition.,Castell A, Short FL, Evans GL, Cookson TV, Bulloch EM, Joseph DD, Lee CE, Parker EJ, Baker EN, Lott JS Biochemistry. 2013 Jan 30. PMID:23363292<ref>PMID:23363292</ref>
-[[3twp]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TWP OCA].
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
 ==See Also==
 *[[Phosphoribosyltransferase|Phosphoribosyltransferase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:023363292</ref><references group="xtra"/><references/>
+__TOC__
-[[Category: Anthranilate phosphoribosyltransferase]]
+</StructureSection>
-[[Category: Castell, A.]]
-[[Category: Lott, J S.]]
-[[Category: Short, F L.]]
 [[Category: Anthranilate phosphoribosyltransferase]]
+[[Category: Castell, A]]
+[[Category: Lott, J S]]
+[[Category: Short, F L]]
 [[Category: Anthranilic acid]]
 [[Category: Magnesium binding phosphoribosyl pyrophosphate]]
 [[Category: Transferase]]
 [[Category: Transferase-transferase inhibitor complex]]