5cwa: Difference between revisions
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==Structure of Anthranilate Synthase Component I (TrpE) from Mycobacterium tuberculosis with inhibitor bound== | |||
<StructureSection load='5cwa' size='340' side='right'caption='[[5cwa]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5cwa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4pen 4pen]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CWA FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0GA:3-{[(1Z)-1-CARBOXYPROP-1-EN-1-YL]OXY}-2-HYDROXYBENZOIC+ACID'>0GA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5cwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cwa OCA], [https://pdbe.org/5cwa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cwa RCSB], [https://www.ebi.ac.uk/pdbsum/5cwa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cwa ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TRPE_MYCTO TRPE_MYCTO] Part of a heterotetrameric complex that catalyzes the two-step biosynthesis of anthranilate, an intermediate in the biosynthesis of L-tryptophan. In the first step, the glutamine-binding beta subunit (TrpG) of anthranilate synthase (AS) provides the glutamine amidotransferase activity which generates ammonia as a substrate that, along with chorismate, is used in the second step, catalyzed by the large alpha subunit of AS (TrpE) to produce anthranilate. In the absence of TrpG, TrpE can synthesize anthranilate directly from chorismate and high concentrations of ammonia (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The tryptophan-biosynthesis pathway is essential for Mycobacterium tuberculosis (Mtb) to cause disease, but not all of the enzymes that catalyse this pathway in this organism have been identified. The structure and function of the enzyme complex that catalyses the first committed step in the pathway, the anthranilate synthase (AS) complex, have been analysed. It is shown that the open reading frames Rv1609 (trpE) and Rv0013 (trpG) encode the chorismate-utilizing (AS-I) and glutamine amidotransferase (AS-II) subunits of the AS complex, respectively. Biochemical assays show that when these subunits are co-expressed a bifunctional AS complex is obtained. Crystallization trials on Mtb-AS unexpectedly gave crystals containing only AS-I, presumably owing to its selective crystallization from solutions containing a mixture of the AS complex and free AS-I. The three-dimensional structure reveals that Mtb-AS-I dimerizes via an interface that has not previously been seen in AS complexes. As is the case in other bacteria, it is demonstrated that Mtb-AS shows cooperative allosteric inhibition by tryptophan, which can be rationalized based on interactions at this interface. Comparative inhibition studies on Mtb-AS-I and related enzymes highlight the potential for single inhibitory compounds to target multiple chorismate-utilizing enzymes for TB drug discovery. | |||
Structure and inhibition of subunit I of the anthranilate synthase complex of Mycobacterium tuberculosis and expression of the active complex.,Bashiri G, Johnston JM, Evans GL, Bulloch EM, Goldstone DC, Jirgis EN, Kleinboelting S, Castell A, Ramsay RJ, Manos-Turvey A, Payne RJ, Lott JS, Baker EN Acta Crystallogr D Biol Crystallogr. 2015 Nov 1;71(Pt 11):2297-308. doi:, 10.1107/S1399004715017216. Epub 2015 Oct 31. PMID:26527146<ref>PMID:26527146</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5cwa" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis CDC1551]] | |||
[[Category: Baker EN]] | |||
[[Category: Bashiri G]] | |||
[[Category: Evans GL]] | |||
[[Category: Johnston JM]] | |||
[[Category: Lott JS]] | |||
Latest revision as of 11:41, 27 September 2023
Structure of Anthranilate Synthase Component I (TrpE) from Mycobacterium tuberculosis with inhibitor boundStructure of Anthranilate Synthase Component I (TrpE) from Mycobacterium tuberculosis with inhibitor bound
Structural highlights
FunctionTRPE_MYCTO Part of a heterotetrameric complex that catalyzes the two-step biosynthesis of anthranilate, an intermediate in the biosynthesis of L-tryptophan. In the first step, the glutamine-binding beta subunit (TrpG) of anthranilate synthase (AS) provides the glutamine amidotransferase activity which generates ammonia as a substrate that, along with chorismate, is used in the second step, catalyzed by the large alpha subunit of AS (TrpE) to produce anthranilate. In the absence of TrpG, TrpE can synthesize anthranilate directly from chorismate and high concentrations of ammonia (By similarity). Publication Abstract from PubMedThe tryptophan-biosynthesis pathway is essential for Mycobacterium tuberculosis (Mtb) to cause disease, but not all of the enzymes that catalyse this pathway in this organism have been identified. The structure and function of the enzyme complex that catalyses the first committed step in the pathway, the anthranilate synthase (AS) complex, have been analysed. It is shown that the open reading frames Rv1609 (trpE) and Rv0013 (trpG) encode the chorismate-utilizing (AS-I) and glutamine amidotransferase (AS-II) subunits of the AS complex, respectively. Biochemical assays show that when these subunits are co-expressed a bifunctional AS complex is obtained. Crystallization trials on Mtb-AS unexpectedly gave crystals containing only AS-I, presumably owing to its selective crystallization from solutions containing a mixture of the AS complex and free AS-I. The three-dimensional structure reveals that Mtb-AS-I dimerizes via an interface that has not previously been seen in AS complexes. As is the case in other bacteria, it is demonstrated that Mtb-AS shows cooperative allosteric inhibition by tryptophan, which can be rationalized based on interactions at this interface. Comparative inhibition studies on Mtb-AS-I and related enzymes highlight the potential for single inhibitory compounds to target multiple chorismate-utilizing enzymes for TB drug discovery. Structure and inhibition of subunit I of the anthranilate synthase complex of Mycobacterium tuberculosis and expression of the active complex.,Bashiri G, Johnston JM, Evans GL, Bulloch EM, Goldstone DC, Jirgis EN, Kleinboelting S, Castell A, Ramsay RJ, Manos-Turvey A, Payne RJ, Lott JS, Baker EN Acta Crystallogr D Biol Crystallogr. 2015 Nov 1;71(Pt 11):2297-308. doi:, 10.1107/S1399004715017216. Epub 2015 Oct 31. PMID:26527146[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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