This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
4nkk
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4nkk is ON HOLD Authors: Yedidi, R.S., Proteasa, G., Kovari, L.C. Description: Crystal structure of multidrug-resistant HIV-1 protease in complex w...) |
|||
| (8 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of a multi-drug resistant clinical isolate-769 HIV-1 protease variant that is resistant to the dimerization inhibitory activity of TLF-PafF== | |
| + | <StructureSection load='4nkk' size='340' side='right'caption='[[4nkk]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <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='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='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> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q000H7_9HIV1 Q000H7_9HIV1] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:25108107</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4nkk" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human immunodeficiency virus 1]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Kovari LC]] | ||
| + | [[Category: Proteasa G]] | ||
| + | [[Category: Yedidi RS]] | ||
Current revision
Crystal structure of a multi-drug resistant clinical isolate-769 HIV-1 protease variant that is resistant to the dimerization inhibitory activity of TLF-PafF
| |||||||||||
