|
|
| Line 3: |
Line 3: |
| | <StructureSection load='2oi2' size='340' side='right'caption='[[2oi2]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='2oi2' size='340' side='right'caption='[[2oi2]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2oi2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"diplococcus_pneumoniae"_(klein_1884)_weichselbaum_1886 "diplococcus pneumoniae" (klein 1884) weichselbaum 1886]. 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> | + | <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='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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mvk ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1313 "Diplococcus pneumoniae" (Klein 1884) Weichselbaum 1886])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Mevalonate_kinase Mevalonate kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.36 2.7.1.36] </span></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> | | <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> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A0H2UNK6_STRPN A0A0H2UNK6_STRPN] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 36: |
Line 37: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mevalonate kinase]] | + | [[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]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
A0A0H2UNK6_STRPN
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 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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Andreassi JL 2nd, Bilder PW, Vetting MW, Roderick SL, Leyh TS. Crystal structure of the Streptococcus pneumoniae mevalonate kinase in complex with diphosphomevalonate. Protein Sci. 2007 May;16(5):983-9. Epub 2007 Mar 30. PMID:17400916 doi:10.1110/ps.072755707
|
