3f0d: Difference between revisions
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 1: | Line 1: | ||
==High resolution crystal structure of 2C-methyl-D-erythritol 2,4-cyclodiphosphatase synthase from Burkholderia pseudomallei== | ==High resolution crystal structure of 2C-methyl-D-erythritol 2,4-cyclodiphosphatase synthase from Burkholderia pseudomallei== | ||
<StructureSection load='3f0d' size='340' side='right' caption='[[3f0d]], [[Resolution|resolution]] 1.20Å' scene=''> | <StructureSection load='3f0d' size='340' side='right'caption='[[3f0d]], [[Resolution|resolution]] 1.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3f0d]] is a 6 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3f0d]] is a 6 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=3F0D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F0D FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=3f0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f0d OCA], [https://pdbe.org/3f0d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f0d RCSB], [https://www.ebi.ac.uk/pdbsum/3f0d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f0d ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 32: | Line 31: | ||
==See Also== | ==See Also== | ||
*[[MECDP synthase|MECDP synthase]] | *[[MECDP synthase 3D structures|MECDP synthase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Burkholderia pseudomallei]] | [[Category: Burkholderia pseudomallei]] | ||
[[Category: | [[Category: Large Structures]] | ||
Latest revision as of 03:27, 28 December 2023
High resolution crystal structure of 2C-methyl-D-erythritol 2,4-cyclodiphosphatase synthase from Burkholderia pseudomalleiHigh resolution crystal structure of 2C-methyl-D-erythritol 2,4-cyclodiphosphatase synthase from Burkholderia pseudomallei
Structural highlights
FunctionISPF_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 Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAs 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||