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.


4ypo

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (13:04, 1 March 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
==Crystal structure of Mycobacterium tuberculosis ketol-acid reductoisomerase in complex with Mg2+==
==Crystal structure of Mycobacterium tuberculosis ketol-acid reductoisomerase in complex with Mg2+==
-
<StructureSection load='4ypo' size='340' side='right' caption='[[4ypo]], [[Resolution|resolution]] 1.00&Aring;' scene=''>
+
<StructureSection load='4ypo' size='340' side='right'caption='[[4ypo]], [[Resolution|resolution]] 1.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[4ypo]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YPO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YPO FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[4ypo]] is a 2 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=4YPO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YPO FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.001&#8491;</td></tr>
-
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ketol-acid_reductoisomerase Ketol-acid reductoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.86 1.1.1.86] </span></td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ypo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ypo OCA], [http://pdbe.org/4ypo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ypo RCSB], [http://www.ebi.ac.uk/pdbsum/4ypo PDBsum]</span></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=4ypo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ypo OCA], [https://pdbe.org/4ypo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ypo RCSB], [https://www.ebi.ac.uk/pdbsum/4ypo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ypo ProSAT]</span></td></tr>
</table>
</table>
-
<div style="background-color:#fffaf0;">
+
== Function ==
-
== Publication Abstract from PubMed ==
+
[https://www.uniprot.org/uniprot/ILVC_MYCTU ILVC_MYCTU] Involved in the biosynthesis of branched-chain amino acids (BCAA). Catalyzes an alkyl-migration followed by a ketol-acid reduction of (S)-2-acetolactate (S2AL) to yield (R)-2,3-dihydroxy-isovalerate. In the isomerase reaction, S2AL is rearranged via a Mg-dependent methyl migration to produce 3-hydroxy-3-methyl-2-ketobutyrate (HMKB). In the reductase reaction, this 2-ketoacid undergoes a metal-dependent reduction by NADPH to yield (R)-2,3-dihydroxy-isovalerate. It is also able to use 3-hydroxypyruvate (HP).<ref>PMID:26876563</ref>
-
The biosynthetic pathway for the branched-chain amino acids is present in plants, fungi and bacteria, but not in animals, making it an attractive target for herbicidal and antimicrobial drug discovery. Ketol-acid reductoisomerase (KARI; EC 1.1.1.86) is the second enzyme in this pathway, converting in a Mg2+ - and NADPH-dependent reaction either 2-acetolactate or 2-aceto-2-hydroxybutyrate to their corresponding 2,3-dihydroxy-3-alkylbutyrate products. Here, we have determined the crystal structure of Mycobacterium tuberculosis KARI (Mt KARI), a class I KARI, with two magnesium ions bound in the active site. X-ray data were obtained to 1.0 A resolution and the final model has an Rfree of 0.174. The structure shows that the active site is solvent-accessible with the two metal ions separated by 4.7 A. A comparison of this structure with that of Mg2+ -free Pseudomonas aeruginosa KARI suggests that upon magnesium binding no movement of the N-domain relative to the C-domain occurs. However, upon formation of the Michaelis complex, as illustrated in the structure of Slackia exigua KARI in complex with NADH.Mg2+ .N-hydroxy-N-isopropyloxamate (IpOHA, a transition state analog), domain movements and reduction of the metal-metal distance to 3.5 A are observed. This inherent flexibility therefore appears to be critical for initiation of the KARI-catalyzed reaction. This study provides new insights into the complex structural rearrangements required for activity of KARIs, particularly those belonging to class I, and provides the framework for the rational design of Mt KARI inhibitors that can be tested as novel antituberculosis agents. This article is protected by copyright. All rights reserved.
+
-
Crystal structure of Mycobacterium tuberculosis ketol-acid reductoisomerase at 1.0 A resolution: A potential target for anti-tuberculosis drug discovery.,Lv Y, Kandale A, Wun SJ, McGeary RP, Williams SJ, Kobe B, Sieber V, Schembri MA, Schenk G, Guddat LW FEBS J. 2016 Feb 15. doi: 10.1111/febs.13672. PMID:26876563<ref>PMID:26876563</ref>
+
==See Also==
-
 
+
*[[Ketol-acid reductoisomerase 3D structures|Ketol-acid reductoisomerase 3D structures]]
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 4ypo" style="background-color:#fffaf0;"></div>
+
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Ketol-acid reductoisomerase]]
+
[[Category: Large Structures]]
-
[[Category: Guddat, L W]]
+
[[Category: Mycobacterium tuberculosis]]
-
[[Category: Lv, Y]]
+
[[Category: Guddat LW]]
-
[[Category: Branch chain amino acid]]
+
[[Category: Lv Y]]
-
[[Category: Ilvc]]
+
-
[[Category: Knotted protein]]
+
-
[[Category: Oxidoreductase]]
+
-
[[Category: Rossmann fold]]
+

Current revision

Crystal structure of Mycobacterium tuberculosis ketol-acid reductoisomerase in complex with Mg2+

PDB ID 4ypo

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/4ypo"
Personal tools