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| | <StructureSection load='5hn9' size='340' side='right'caption='[[5hn9]], [[Resolution|resolution]] 2.12Å' scene=''> | | <StructureSection load='5hn9' size='340' side='right'caption='[[5hn9]], [[Resolution|resolution]] 2.12Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hn9]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Plavs Plavs]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HN9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HN9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5hn9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_vivax_Sal-1 Plasmodium vivax Sal-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HN9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HN9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=04W:2-{[3-(DECYLOXY)BENZYL]OXY}-5-NITROBENZOIC+ACID'>04W</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]] 2.12Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hn7|5hn7]], [[5hn8|5hn8]], [[5hna|5hna]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=04W:2-{[3-(DECYLOXY)BENZYL]OXY}-5-NITROBENZOIC+ACID'>04W</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PVX_092040 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=126793 PLAVS])</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=5hn9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hn9 OCA], [https://pdbe.org/5hn9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hn9 RCSB], [https://www.ebi.ac.uk/pdbsum/5hn9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hn9 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5hn9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hn9 OCA], [http://pdbe.org/5hn9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hn9 RCSB], [http://www.ebi.ac.uk/pdbsum/5hn9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hn9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A5K4U6_PLAVS A5K4U6_PLAVS] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Plavs]] | + | [[Category: Plasmodium vivax Sal-1]] |
| - | [[Category: Liu, Y L]] | + | [[Category: Liu Y-L]] |
| - | [[Category: OIdfield, E]] | + | [[Category: OIdfield E]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Zhang Y]] |
| - | [[Category: All helice]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| Structural highlights
Function
A5K4U6_PLAVS
Publication Abstract from PubMed
We report a molecular dynamics investigation of the structure, function, and inhibition of geranylgeranyl diphosphate synthase (GGPPS), a potential drug target, from the malaria parasite Plasmodium vivax. We discovered several GGPPS inhibitors, benzoic acids, and determined their structures crystallographically. We then used molecular dynamics simulations to investigate the dynamics of three such inhibitors and two bisphosphonate inhibitors, zoledronate and a lipophilic analogue of zoledronate, as well as the enzyme's product, GGPP. We were able to identify the main motions that govern substrate binding and product release as well as the molecular features required for GGPPS inhibition by both classes of inhibitor. The results are of broad general interest because they represent the first detailed investigation of the mechanism of action, and inhibition, of an important antimalarial drug target, geranylgeranyl diphosphate synthase, and may help guide the development of other, novel inhibitors as new drug leads.
Dynamic Structure and Inhibition of a Malaria Drug Target: Geranylgeranyl Diphosphate Synthase.,G Ricci C, Liu YL, Zhang Y, Wang Y, Zhu W, Oldfield E, McCammon JA Biochemistry. 2016 Sep 1. PMID:27564465[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ G Ricci C, Liu YL, Zhang Y, Wang Y, Zhu W, Oldfield E, McCammon JA. Dynamic Structure and Inhibition of a Malaria Drug Target: Geranylgeranyl Diphosphate Synthase. Biochemistry. 2016 Sep 1. PMID:27564465 doi:http://dx.doi.org/10.1021/acs.biochem.6b00398
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