5j5d: Difference between revisions

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-'''Unreleased structure'''
-The entry 5j5d is ON HOLD
+==Crystal structure of Dihydrodipicolinate Synthase from Mycobacterium tuberculosis in complex with alpha-ketopimelic acid==
+<StructureSection load='5j5d' size='340' side='right'caption='[[5j5d]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5j5d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J5D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J5D 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]] 2.4&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6GT:2-OXOHEPTANEDIOIC+ACID'>6GT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5j5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5d OCA], [https://pdbe.org/5j5d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j5d RCSB], [https://www.ebi.ac.uk/pdbsum/5j5d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5d ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DAPA_MYCTU DAPA_MYCTU] Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA) (Probable).<ref>PMID:18062777</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The Mycobacterium tuberculosis dihydrodipicolinate synthase (Mtb-dapA) is an essential gene. Mtb-DapA catalyzes the aldol condensation between pyruvate and L-aspartate-beta-semialdehyde (ASA) to yield dihydrodipicolinate. In this work we tested the inhibitory effects of structural analogues of pyruvate on recombinant Mtb-DapA (Mtb-rDapA) using a coupled assay with recombinant dihydrodipicolinate reductase (Mtb-rDapB). Alpha-ketopimelic acid (alpha-KPA) showed maximum inhibition of 88% and IC50 of 21 muM in the presence of pyruvate (500 muM) and ASA (400 muM). Competition experiments with pyruvate and ASA revealed competition of alpha-KPA with pyruvate. Liquid chromatography-mass spectrometry (LC-MS) data with multiple reaction monitoring (MRM) showed that the relative abundance peak of final product, 2,3,4,5-tetrahydrodipicolinate, was decreased by 50%. Thermal shift assays showed 1 degrees C Tm shift of Mtb-rDapA upon binding alpha-KPA. The 2.4 A crystal structure of Mtb-rDapA-alpha-KPA complex showed the interaction of critical residues at the active site with alpha-KPA. Molecular dynamics simulations over 500 ns of pyruvate docked to Mtb-DapA and of alpha-KPA-bound Mtb-rDapA revealed formation of hydrogen bonds with pyruvate throughout in contrast to alpha-KPA. Molecular descriptors analysis showed that ligands with polar surface area of 91.7 A(2) are likely inhibitors. In summary, alpha-hydroxypimelic acid and other analogues could be explored further as inhibitors of Mtb-DapA.
-Authors:
+Inhibition of Mycobacterium tuberculosis dihydrodipicolinate synthase by alpha-ketopimelic acid and its other structural analogues.,Shrivastava P, Navratna V, Silla Y, Dewangan RP, Pramanik A, Chaudhary S, Rayasam G, Kumar A, Gopal B, Ramachandran S Sci Rep. 2016 Aug 9;6:30827. doi: 10.1038/srep30827. PMID:27501775<ref>PMID:27501775</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5j5d" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Dihydrodipicolinate synthase|Dihydrodipicolinate synthase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
+[[Category: Gopal B]]
+[[Category: Navratna V]]