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| | <StructureSection load='4nkk' size='340' side='right'caption='[[4nkk]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='4nkk' size='340' side='right'caption='[[4nkk]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4nkk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NKK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NKK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4nkk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NKK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NKK FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pj6|3pj6]], [[1tw7|1tw7]]</td></tr> | + | </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=4nkk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nkk OCA], [https://pdbe.org/4nkk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nkk RCSB], [https://www.ebi.ac.uk/pdbsum/4nkk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nkk ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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=4nkk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nkk OCA], [http://pdbe.org/4nkk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nkk RCSB], [http://www.ebi.ac.uk/pdbsum/4nkk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nkk ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q000H7_9HIV1 Q000H7_9HIV1] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Human immunodeficiency virus 1]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kovari, L C]] | + | [[Category: Kovari LC]] |
| - | [[Category: Proteasa, G]] | + | [[Category: Proteasa G]] |
| - | [[Category: Yedidi, R S]] | + | [[Category: Yedidi RS]] |
| - | [[Category: Aid]]
| + | |
| - | [[Category: Clinical isolate 769]]
| + | |
| - | [[Category: Dimer protease]]
| + | |
| - | [[Category: Dimerization inhibitor]]
| + | |
| - | [[Category: Hiv]]
| + | |
| - | [[Category: Hiv-1 protease]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Multidrug-resistance]]
| + | |
| - | [[Category: Protease inhibitor]]
| + | |
| Structural highlights
Function
Q000H7_9HIV1
Publication Abstract from PubMed
Human immunodeficiency virus type-1 (HIV-1) protease, a homodimeric aspartyl protease, is a critical drug target in designing anti-retroviral drugs to treat HIV/AIDS. Multidrug-resistant (MDR) clinical isolate-769 HIV-1 protease (PDB ID: 3PJ6) has been shown to exhibit expanded active site cavity with wide-open conformation of flaps (Gly48-Gly52) due to the accumulation of multiple mutations. In this study, an HIV-1 protease dimerization inhibitor (PDI)-TLF-PafF, was evaluated against MDR769 HIV-1 protease using X-ray crystallography. It was hypothesized that co-crystallization of MDR769 HIV-1 protease in complex with TLF-PafF would yield either a monomeric or a disrupted dimeric structure. However, crystal structure of MDR769 I10V HIV-1 protease co-crystallized with TLF-PafF revealed an undisrupted dimeric protease structure (PDB ID: 4NKK) that is comparable to the crystal structure of its corresponding apo-protease (PDB ID: 3PJ6). In order to understand the binding profile of TLF-PafF as a PDI, docking analysis was performed using monomeric protease (prepared from the dimeric crystal structure, PDB ID: 4NKK) as docking receptor. Docking analysis revealed that TLF-PafF binds at the N and C termini (dimerization domain) in a clamp shape for the monomeric wild type receptor but not the MDR769 monomeric receptor. TLF-PafF preferentially showed higher binding affinity to the expanded active site cavity of MDR769 HIV-1 protease than to the termini. Irrespective of binding location, the binding affinity of TLF-PafF against wild type receptor (-6.7kcal/mol) was found to be higher compared to its corresponding binding affinity against MDR receptor (-4.6kcal/mol) suggesting that the MDR769 HIV-1 protease could be resistant to the PDI-activity of TLF-PafF, thus supporting the dimeric crystal structure (PDB ID: 4NKK).
A multi-drug resistant HIV-1 protease is resistant to the dimerization inhibitory activity of TLF-PafF.,Yedidi RS, Proteasa G, Martin PD, Liu Z, Vickrey JF, Kovari IA, Kovari LC J Mol Graph Model. 2014 Jul 4;53C:105-111. doi: 10.1016/j.jmgm.2014.06.010. PMID:25108107[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yedidi RS, Proteasa G, Martin PD, Liu Z, Vickrey JF, Kovari IA, Kovari LC. A multi-drug resistant HIV-1 protease is resistant to the dimerization inhibitory activity of TLF-PafF. J Mol Graph Model. 2014 Jul 4;53C:105-111. doi: 10.1016/j.jmgm.2014.06.010. PMID:25108107 doi:http://dx.doi.org/10.1016/j.jmgm.2014.06.010
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