This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


6s7k

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: '''Unreleased structure''' The entry 6s7k is ON HOLD until Paper Publication Authors: Whitehouse, A.J., Libardo, M.D., Kasbekar, M., Brear, P., Fischer, G., Thomas, C.J., Barry, C.E., B...)
Current revision (12:36, 24 January 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 6s7k is ON HOLD until Paper Publication
+
==Fumarate hydratase of Mycobacterium tuberculosis in complex with formate and allosteric modulator N-(2-Methoxy-5-(N-methylsulfamoyl)phenyl)-2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetamide==
 +
<StructureSection load='6s7k' size='340' side='right'caption='[[6s7k]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[6s7k]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S7K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6S7K 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]] 1.55&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=KYZ:~{N}-[2-methoxy-5-(methylsulfamoyl)phenyl]-2-(4-oxidanylidene-3~{H}-phthalazin-1-yl)ethanamide'>KYZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6s7k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s7k OCA], [https://pdbe.org/6s7k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6s7k RCSB], [https://www.ebi.ac.uk/pdbsum/6s7k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6s7k ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/FUMC_MYCTU FUMC_MYCTU] Catalyzes the reversible addition of water to fumarate to give L-malate.
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
With the growing worldwide prevalence of antibiotic-resistant strains of tuberculosis (TB), new targets are urgently required for the development of treatments with novel modes of action. Fumarate hydratase (fumarase), a vulnerable component of the citric acid cycle in Mycobacterium tuberculosis (Mtb), is a metabolic target that could satisfy this unmet demand. A key challenge in the targeting of Mtb fumarase is its similarity to the human homolog, which shares an identical active site. A potential solution to this selectivity problem was previously found in a high-throughput screening hit that binds in a nonconserved allosteric site. In this work, a structure-activity relationship study was carried out with the determination of further structural biology on the lead series, affording derivatives with sub-micromolar inhibition. Further, the screening of this series against Mtb in vitro identified compounds with potent minimum inhibitory concentrations.
-
Authors: Whitehouse, A.J., Libardo, M.D., Kasbekar, M., Brear, P., Fischer, G., Thomas, C.J., Barry, C.E., Boshoff, H.I., Coyne, A.G., Abell, C.
+
Targeting of Fumarate Hydratase from Mycobacterium tuberculosis Using Allosteric Inhibitors with a Dimeric-Binding Mode.,Whitehouse AJ, Libardo MDJ, Kasbekar M, Brear PD, Fischer G, Thomas CJ, Barry CE 3rd, Boshoff HIM, Coyne AG, Abell C J Med Chem. 2019 Dec 12;62(23):10586-10604. doi: 10.1021/acs.jmedchem.9b01203., Epub 2019 Sep 27. PMID:31517489<ref>PMID:31517489</ref>
-
Description: Fumarate hydratase of Mycobacterium tuberculosis in complex with formate and allosteric modulator N-(2-Methoxy-5-(N-methylsulfamoyl)phenyl)-2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
-
[[Category: Thomas, C.J]]
+
<div class="pdbe-citations 6s7k" style="background-color:#fffaf0;"></div>
-
[[Category: Kasbekar, M]]
+
 
-
[[Category: Fischer, G]]
+
==See Also==
-
[[Category: Abell, C]]
+
*[[Fumarase|Fumarase]]
-
[[Category: Brear, P]]
+
== References ==
-
[[Category: Whitehouse, A.J]]
+
<references/>
-
[[Category: Coyne, A.G]]
+
__TOC__
-
[[Category: Libardo, M.D]]
+
</StructureSection>
-
[[Category: Boshoff, H.I]]
+
[[Category: Large Structures]]
-
[[Category: Barry, C.E]]
+
[[Category: Mycobacterium tuberculosis]]
 +
[[Category: Abell C]]
 +
[[Category: Barry CE]]
 +
[[Category: Boshoff HI]]
 +
[[Category: Brear P]]
 +
[[Category: Coyne AG]]
 +
[[Category: Fischer G]]
 +
[[Category: Kasbekar M]]
 +
[[Category: Libardo MD]]
 +
[[Category: Thomas CJ]]
 +
[[Category: Whitehouse AJ]]

Current revision

Fumarate hydratase of Mycobacterium tuberculosis in complex with formate and allosteric modulator N-(2-Methoxy-5-(N-methylsulfamoyl)phenyl)-2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetamide

PDB ID 6s7k

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6s7k"
Personal tools