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< | ==Structure of 2C-Methyl-D-erythritol-2,4-cyclodiphosphate Synthase== | ||
<StructureSection load='1gx1' size='340' side='right'caption='[[1gx1]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1gx1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_BL21 Escherichia coli BL21]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GX1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GX1 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]] 1.8Å</td></tr> | |||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CDP:CYTIDINE-5-DIPHOSPHATE'>CDP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1gx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gx1 OCA], [https://pdbe.org/1gx1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gx1 RCSB], [https://www.ebi.ac.uk/pdbsum/1gx1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gx1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ISPF_ECOLI ISPF_ECOLI] 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). Also converts 4-diphosphocytidyl-2-C-methyl-D-erythritol into 2-C-methyl-D-erythritol 3,4-cyclophosphate and CMP.<ref>PMID:10694574</ref> <ref>PMID:22839733</ref> | |||
== 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/gx/1gx1_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1gx1 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The crystal structure of the zinc enzyme Escherichia coli 2C-methyl-d-erythritol 2,4-cyclodiphosphate synthase in complex with cytidine 5'-diphosphate and Mn(2+) has been determined to 1.8-A resolution. This enzyme is essential in E. coli and participates in the nonmevalonate pathway of isoprenoid biosynthesis, a critical pathway present in some bacterial and apicomplexans but distinct from that used by mammals. Our analysis reveals a homotrimer, built around a beta prism, carrying three active sites, each of which is formed in a cleft between pairs of subunits. Residues from two subunits recognize and bind the nucleotide in an active site that contains a Zn(2+) with tetrahedral coordination. A Mn(2+), with octahedral geometry, is positioned between the alpha and beta phosphates acting in concert with the Zn(2+) to align and polarize the substrate for catalysis. A high degree of sequence conservation for the enzymes from E. coli, Plasmodium falciparum, and Mycobacterium tuberculosis suggests similarities in secondary structure, subunit fold, quaternary structure, and active sites. Our model will therefore serve as a template to facilitate the structure-based design of potential antimicrobial agents targeting two of the most serious human diseases, tuberculosis and malaria. | |||
Structure of 2C-methyl-D-erythritol 2,4- cyclodiphosphate synthase: an essential enzyme for isoprenoid biosynthesis and target for antimicrobial drug development.,Kemp LE, Bond CS, Hunter WN Proc Natl Acad Sci U S A. 2002 May 14;99(10):6591-6. Epub 2002 May 7. PMID:11997478<ref>PMID:11997478</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1gx1" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[MECDP synthase|MECDP synthase]] | |||
*[[MECDP synthase 3D structures|MECDP synthase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
== | </StructureSection> | ||
[[Category: Escherichia coli BL21]] | |||
[[Category: Large Structures]] | |||
== | [[Category: Bond CS]] | ||
[[Category: Hunter WN]] | |||
[[Category: Kemp LE]] | |||
[[Category: Escherichia coli]] | |||
[[Category: | |||
[[Category: Bond | |||
[[Category: Hunter | |||
[[Category: Kemp | |||
Latest revision as of 03:01, 21 November 2024
Structure of 2C-Methyl-D-erythritol-2,4-cyclodiphosphate SynthaseStructure of 2C-Methyl-D-erythritol-2,4-cyclodiphosphate Synthase
Structural highlights
FunctionISPF_ECOLI 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). Also converts 4-diphosphocytidyl-2-C-methyl-D-erythritol into 2-C-methyl-D-erythritol 3,4-cyclophosphate and CMP.[1] [2] 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 PubMedThe crystal structure of the zinc enzyme Escherichia coli 2C-methyl-d-erythritol 2,4-cyclodiphosphate synthase in complex with cytidine 5'-diphosphate and Mn(2+) has been determined to 1.8-A resolution. This enzyme is essential in E. coli and participates in the nonmevalonate pathway of isoprenoid biosynthesis, a critical pathway present in some bacterial and apicomplexans but distinct from that used by mammals. Our analysis reveals a homotrimer, built around a beta prism, carrying three active sites, each of which is formed in a cleft between pairs of subunits. Residues from two subunits recognize and bind the nucleotide in an active site that contains a Zn(2+) with tetrahedral coordination. A Mn(2+), with octahedral geometry, is positioned between the alpha and beta phosphates acting in concert with the Zn(2+) to align and polarize the substrate for catalysis. A high degree of sequence conservation for the enzymes from E. coli, Plasmodium falciparum, and Mycobacterium tuberculosis suggests similarities in secondary structure, subunit fold, quaternary structure, and active sites. Our model will therefore serve as a template to facilitate the structure-based design of potential antimicrobial agents targeting two of the most serious human diseases, tuberculosis and malaria. Structure of 2C-methyl-D-erythritol 2,4- cyclodiphosphate synthase: an essential enzyme for isoprenoid biosynthesis and target for antimicrobial drug development.,Kemp LE, Bond CS, Hunter WN Proc Natl Acad Sci U S A. 2002 May 14;99(10):6591-6. Epub 2002 May 7. PMID:11997478[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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