View source for 3zgn


==Crystal structures of Escherichia coli IspH in complex with TMBPP a potent inhibitor of the methylerythritol phosphate pathway==
<StructureSection load='3zgn' size='340' side='right'caption='[[3zgn]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zgn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZGN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZGN 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]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=10G:(2E)-3-METHYL-4-SULFANYLBUT-2-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>10G</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=3zgn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zgn OCA], [https://pdbe.org/3zgn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zgn RCSB], [https://www.ebi.ac.uk/pdbsum/3zgn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zgn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ISPH_ECOLI ISPH_ECOLI] Converts 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Is also involved in penicillin tolerance and control of the stringent response. Seems to directly or indirectly interact with RelA to maintain it in an inactive form during normal growth.<ref>PMID:19569147</ref> <ref>PMID:20080550</ref> <ref>PMID:22137895</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
IspH, also called LytB, a protein involved in the biosynthesis of isoprenoids through the methylerythritol phosphate pathway, is an attractive target for the development of new antimicrobial drugs. Here, we report crystal structures of Escherichia coli IspH in complex with the two most potent inhibitors: (E)-4-mercapto-3-methylbut-2-en-1-yl diphosphate (TMBPP) and (E)-4-amino-3-methylbut-2-en-1-yl diphosphate (AMBPP) at 1.95 and 1.7 A resolution, respectively. The structure of the E. coli IspH:TMBPP complex exhibited two conformers of the inhibitor. This unexpected feature was exploited to design and evolve new antimicrobial candidates in silico.

Further Insight into Crystal Structures of Escherichia coli IspH/LytB in Complex with Two Potent Inhibitors of the MEP Pathway: A Starting Point for Rational Design of New Antimicrobials.,Borel F, Barbier E, Krasutsky S, Janthawornpong K, Chaignon P, Poulter CD, Ferrer JL, Seemann M Chembiochem. 2017 Nov 2;18(21):2137-2144. doi: 10.1002/cbic.201700363. Epub 2017 , Oct 2. PMID:28862365<ref>PMID:28862365</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3zgn" style="background-color:#fffaf0;"></div>

==See Also==
*[[4-hydroxy-3-methylbut-2-enyl diphosphate reductase 3D structures|4-hydroxy-3-methylbut-2-enyl diphosphate reductase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Barbier E]]
[[Category: Borel F]]
[[Category: Dale Poulter C]]
[[Category: Ferrer JL]]
[[Category: Janthawornpong K]]
[[Category: Kratsutsky S]]
[[Category: Rohmer M]]
[[Category: Seemann M]]