View source for 4asy


==Pseudomonas aeruginosa RmlA in complex with allosteric inhibitor==
<StructureSection load='4asy' size='340' side='right'caption='[[4asy]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4asy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ASY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ASY 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]] 2.3&#8491;</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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=N5Y:N-(6-AMINO-1-BENZYL-2,4-DIOXO-1,2,3,4-TETRAHYDROPYRIMIDIN-5-YL)-N-METHYLBENZAMIDE'>N5Y</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=4asy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4asy OCA], [https://pdbe.org/4asy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4asy RCSB], [https://www.ebi.ac.uk/pdbsum/4asy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4asy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9HU22_PSEAE Q9HU22_PSEAE] Catalyzes the formation of dTDP-glucose, from dTTP and glucose 1-phosphate, as well as its pyrophosphorolysis (By similarity).[RuleBase:RU003706]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glucose-1-phosphate thymidylyltransferase (RmlA) catalyzes the condensation of glucose-1-phosphate (G1P) with deoxy-thymidine tri-phosphate (dTTP) to yield dTDP-L-rhamnose and pyrophosphate. This is the first step in the L-rhamnose biosynthetic pathway. L-rhamnose is an important component of the cell wall of many microorganisms, including Mycobacterium tuberculosis and Pseudomonas aeruginosa. Here we describe the first nanomolar inhibitors of P. aeruginosa RmlA. These thymine analogs were identified by high-throughput screening and subsequently optimized by a combination of protein crystallography, in silico screening and synthetic chemistry. Some of the inhibitors show inhibitory activity against M. tuberculosis. The inhibitors do not bind at the active site of RmlA but bind at a second site remote from the active site. Despite this, the compounds act as competitive inhibitors of G1P but with high cooperativity. This novel behavior was probed by structural analysis which suggests that the inhibitors work by preventing RmlA from undergoing the conformational change key to its ordered bi-bi mechanism.

Allosteric Competitive Inhibitors of the Glucose-1-Phosphate Thymidylyltransferase (RmlA) from Pseudomonas aeruginosa.,Alphey MS, Pirrie L, Torrie LS, Boulkeroura WA, Gardiner M, Sarkar A, Maringer M, Oehlmann W, Brenk R, Scherman MS, McNeil M, Rejzek M, Field RA, Singh M, Gray D, Westwood NJ, Naismith JH ACS Chem Biol. 2012 Nov 8. PMID:23138692<ref>PMID:23138692</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4asy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glucose-1-phosphate thymidylyltransferase 3D structures|Glucose-1-phosphate thymidylyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa PAO1]]
[[Category: Alphey MS]]
[[Category: Brenk R]]
[[Category: Gardiner M]]
[[Category: Gray D]]
[[Category: Naismith JH]]
[[Category: Pirrie L]]
[[Category: Sarkar A]]
[[Category: Torrie LS]]
[[Category: Westwood NJ]]