3jvh: Difference between revisions
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< | ==Crystal structure of 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase from Burkholderia pseudomallei with FOL fragment 8395== | ||
<StructureSection load='3jvh' size='340' side='right'caption='[[3jvh]], [[Resolution|resolution]] 1.69Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3jvh]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_pseudomallei Burkholderia pseudomallei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JVH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JVH 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]] 1.69Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HHV:5-[(PYRIDIN-3-YLMETHYL)AMINO]-1H-PYRAZOLE-4-CARBOXAMIDE'>HHV</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3jvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jvh OCA], [https://pdbe.org/3jvh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jvh RCSB], [https://www.ebi.ac.uk/pdbsum/3jvh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jvh ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ISPF_BURP1 ISPF_BURP1] Involved in the biosynthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), two major building blocks of isoprenoid compounds. Catalyzes the conversion of 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-ME2P) to 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-CPP) with a corresponding release of cytidine 5-monophosphate (CMP) (By similarity).[HAMAP-Rule:MF_00107] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jv/3jvh_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3jvh ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
As part of the Seattle Structural Genomics Center for Infectious Disease, we seek to enhance structural genomics with ligand-bound structure data which can serve as a blueprint for structure-based drug design. We have adapted fragment-based screening methods to our structural genomics pipeline to generate multiple ligand-bound structures of high priority drug targets from pathogenic organisms. In this study, we report fragment screening methods and structure determination results for 2C-methyl-D-erythritol-2,4-cyclo-diphosphate (MECP) synthase from Burkholderia pseudomallei, the gram-negative bacterium which causes melioidosis. Screening by nuclear magnetic resonance spectroscopy as well as crystal soaking followed by X-ray diffraction led to the identification of several small molecules which bind this enzyme in a critical metabolic pathway. A series of complex structures obtained with screening hits reveal distinct binding pockets and a range of small molecules which form complexes with the target. Additional soaks with these compounds further demonstrate a subset of fragments to only bind the protein when present in specific combinations. This ensemble of fragment-bound complexes illuminates several characteristics of MECP synthase, including a previously unknown binding surface external to the catalytic active site. These ligand-bound structures now serve to guide medicinal chemists and structural biologists in rational design of novel inhibitors for this enzyme. | |||
Leveraging structure determination with fragment screening for infectious disease drug targets: MECP synthase from Burkholderia pseudomallei.,Begley DW, Hartley RC, Davies DR, Edwards TE, Leonard JT, Abendroth J, Burris CA, Bhandari J, Myler PJ, Staker BL, Stewart LJ J Struct Funct Genomics. 2011 Jul;12(2):63-76. Epub 2011 Feb 26. PMID:21359640<ref>PMID:21359640</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3jvh" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[MECDP synthase 3D structures|MECDP synthase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
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< | |||
[[Category: Burkholderia pseudomallei]] | [[Category: Burkholderia pseudomallei]] | ||
[[Category: | [[Category: Large Structures]] | ||