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[[Image:2oi2.jpg|left|200px]]
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{{STRUCTURE_2oi2|  PDB=2oi2  |  SCENE=  }}
'''Streptococcus pneumoniae Mevalonate Kinase in Complex with Diphosphomevalonate'''


==Streptococcus pneumoniae Mevalonate Kinase in Complex with Diphosphomevalonate==
<StructureSection load='2oi2' size='340' side='right'caption='[[2oi2]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2oi2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OI2 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DP6:(3R)-3-HYDROXY-5-{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]OXY}-3-METHYLPENTANOIC+ACID'>DP6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=2oi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oi2 OCA], [https://pdbe.org/2oi2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oi2 RCSB], [https://www.ebi.ac.uk/pdbsum/2oi2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oi2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0H2UNK6_STRPN A0A0H2UNK6_STRPN]
== 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/oi/2oi2_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=2oi2 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Streptococcus pneumoniae, a ubiquitous gram-positive pathogen with an alarming, steadily evolving resistance to frontline antimicrobials, poses a severe global health threat both in the community and in the clinic. The recent discovery that diphosphomevalonate (DPM), an essential intermediate in the isoprenoid biosynthetic pathway, potently and allosterically inhibits S. pneumoniae mevalonate kinase (SpMK) without affecting the human isozyme established a new target and lead compound for antimicrobial design. Here we present the crystal structure of the first S. pneumoniae mevalonate kinase, at a resolution of 2.5 A and in complex with DPM.Mg(2+) in the active-site cleft. Structural comparison of SpMK with other members of the GHMP kinase family reveals that DPM functions as a partial bisubstrate analog (mevalonate linked to the pyrophosphoryl moiety of ATP) in that it elicits a ternary-complexlike form of the enzyme, except for localized disordering in a region that would otherwise interact with the missing portion of the nucleotide. Features of the SpMK-binding pockets are discussed in the context of established mechanistic findings and inherited human diseases linked to MK deficiency.


==Overview==
Crystal structure of the Streptococcus pneumoniae mevalonate kinase in complex with diphosphomevalonate.,Andreassi JL 2nd, Bilder PW, Vetting MW, Roderick SL, Leyh TS Protein Sci. 2007 May;16(5):983-9. Epub 2007 Mar 30. PMID:17400916<ref>PMID:17400916</ref>
Streptococcus pneumoniae, a ubiquitous gram-positive pathogen with an alarming, steadily evolving resistance to frontline antimicrobials, poses a severe global health threat both in the community and in the clinic. The recent discovery that diphosphomevalonate (DPM), an essential intermediate in the isoprenoid biosynthetic pathway, potently and allosterically inhibits S. pneumoniae mevalonate kinase (SpMK) without affecting the human isozyme established a new target and lead compound for antimicrobial design. Here we present the crystal structure of the first S. pneumoniae mevalonate kinase, at a resolution of 2.5 A and in complex with DPM.Mg(2+) in the active-site cleft. Structural comparison of SpMK with other members of the GHMP kinase family reveals that DPM functions as a partial bisubstrate analog (mevalonate linked to the pyrophosphoryl moiety of ATP) in that it elicits a ternary-complexlike form of the enzyme, except for localized disordering in a region that would otherwise interact with the missing portion of the nucleotide. Features of the SpMK-binding pockets are discussed in the context of established mechanistic findings and inherited human diseases linked to MK deficiency.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2OI2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OI2 OCA].
</div>
<div class="pdbe-citations 2oi2" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Crystal structure of the Streptococcus pneumoniae mevalonate kinase in complex with diphosphomevalonate., Andreassi JL 2nd, Bilder PW, Vetting MW, Roderick SL, Leyh TS, Protein Sci. 2007 May;16(5):983-9. Epub 2007 Mar 30. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17400916 17400916]
*[[Mevalonate kinase|Mevalonate kinase]]
[[Category: Mevalonate kinase]]
== References ==
[[Category: Single protein]]
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptococcus pneumoniae]]
[[Category: Streptococcus pneumoniae]]
[[Category: Andreassi, J L.]]
[[Category: Andreassi JL]]
[[Category: Bilder, P W.]]
[[Category: Bilder PW]]
[[Category: Leyh, T S.]]
[[Category: Leyh TS]]
[[Category: Roderick, S L.]]
[[Category: Roderick SL]]
[[Category: Vetting, M W.]]
[[Category: Vetting MW]]
[[Category: Enzyme-inhibitor complex]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 10:57:57 2008''

Latest revision as of 00:19, 28 December 2023

Streptococcus pneumoniae Mevalonate Kinase in Complex with Diphosphomevalonate

2oi2, resolution 2.50Å

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