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5tcj

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Revision as of 11:29, 16 September 2020

Crystal structure of tryptophan synthase from M. tuberculosis - aminoacrylate and BRD4592-bound form

Structural highlights

5tcj is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	5tcf, 5tcg, 5tch, 5tci
Activity:	Tryptophan synthase, with EC number 4.2.1.20
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TRPA_MYCTU] The alpha subunit is responsible for the aldol cleavage of indoleglycerol phosphate to indole and glyceraldehyde 3-phosphate. [TRPB_MYCTU] The beta subunit is responsible for the synthesis of L-tryptophan from indole and L-serine (By similarity).

Publication Abstract from PubMed

New antibiotics with novel targets are greatly needed. Bacteria have numerous essential functions, but only a small fraction of such processes-primarily those involved in macromolecular synthesis-are inhibited by current drugs. Targeting metabolic enzymes has been the focus of recent interest, but effective inhibitors have been difficult to identify. We describe a synthetic azetidine derivative, BRD4592, that kills Mycobacterium tuberculosis (Mtb) through allosteric inhibition of tryptophan synthase (TrpAB), a previously untargeted, highly allosterically regulated enzyme. BRD4592 binds at the TrpAB alpha-beta-subunit interface and affects multiple steps in the enzyme's overall reaction, resulting in inhibition not easily overcome by changes in metabolic environment. We show that TrpAB is required for the survival of Mtb and Mycobacterium marinum in vivo and that this requirement may be independent of an adaptive immune response. This work highlights the effectiveness of allosteric inhibition for targeting proteins that are naturally highly dynamic and that are essential in vivo, despite their apparent dispensability under in vitro conditions, and suggests a framework for the discovery of a next generation of allosteric inhibitors.

A small-molecule allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase.,Wellington S, Nag PP, Michalska K, Johnston SE, Jedrzejczak RP, Kaushik VK, Clatworthy AE, Siddiqi N, McCarren P, Bajrami B, Maltseva NI, Combs S, Fisher SL, Joachimiak A, Schreiber SL, Hung DT Nat Chem Biol. 2017 Sep;13(9):943-950. doi: 10.1038/nchembio.2420. Epub 2017 Jul , 3. PMID:28671682^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wellington S, Nag PP, Michalska K, Johnston SE, Jedrzejczak RP, Kaushik VK, Clatworthy AE, Siddiqi N, McCarren P, Bajrami B, Maltseva NI, Combs S, Fisher SL, Joachimiak A, Schreiber SL, Hung DT. A small-molecule allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase. Nat Chem Biol. 2017 Sep;13(9):943-950. doi: 10.1038/nchembio.2420. Epub 2017 Jul , 3. PMID:28671682 doi:http://dx.doi.org/10.1038/nchembio.2420

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5tcj"

@@ Line 1: / Line 1: @@
 ==Crystal structure of tryptophan synthase from M. tuberculosis - aminoacrylate and BRD4592-bound form==
-<StructureSection load='5tcj' size='340' side='right' caption='[[5tcj]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='5tcj' size='340' side='right'caption='[[5tcj]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5tcj]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TCJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TCJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5tcj]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TCJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5TCJ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=79V:(2R,3S,4R)-3-(2-fluoro[1,1-biphenyl]-4-yl)-4-(hydroxymethyl)azetidine-2-carbonitrile'>79V</scene>, <scene name='pdbligand=CS:CESIUM+ION'>CS</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=P1T:2-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]ACRYLIC+ACID'>P1T</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=79V:(2R,3S,4R)-3-(2-fluoro[1,1-biphenyl]-4-yl)-4-(hydroxymethyl)azetidine-2-carbonitrile'>79V</scene>, <scene name='pdbligand=CS:CESIUM+ION'>CS</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=P1T:2-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]ACRYLIC+ACID'>P1T</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tcf|5tcf]], [[5tcg|5tcg]], [[5tch|5tch]], [[5tci|5tci]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tryptophan_synthase Tryptophan synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.20 4.2.1.20] </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=5tcj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tcj OCA], [http://pdbe.org/5tcj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tcj RCSB], [http://www.ebi.ac.uk/pdbsum/5tcj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tcj ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5tcj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tcj OCA], [http://pdbe.org/5tcj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tcj RCSB], [http://www.ebi.ac.uk/pdbsum/5tcj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tcj ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 5tcj" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Tryptophan synthase 3D structures|Tryptophan synthase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Tryptophan synthase]]
 [[Category: Structural genomic]]

5tcj

From Proteopedia

Revision as of 11:29, 16 September 2020

Crystal structure of tryptophan synthase from M. tuberculosis - aminoacrylate and BRD4592-bound form

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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