1k6t: Difference between revisions
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[[Image:1k6t.gif|left|200px]] | [[Image:1k6t.gif|left|200px]] | ||
'''LACK OF SYNERGY FOR INHIBITORS TARGETING A MULTI-DRUG RESISTANT HIV-1 PROTEASE''' | {{Structure | ||
|PDB= 1k6t |SIZE=350|CAPTION= <scene name='initialview01'>1k6t</scene>, resolution 2.25Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene> and <scene name='pdbligand=XN1:N-[2-HYDROXY-1-INDANYL]-5-[(2-TERTIARYBUTYLAMINOCARBONYL)-4(3-PYRIDYLMETHYL)PIPERAZINO]-4-HYDROXY-2-(1-PHENYLETHYL)-PENTANAMIDE'>XN1</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] | |||
|GENE= POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | |||
}} | |||
'''LACK OF SYNERGY FOR INHIBITORS TARGETING A MULTI-DRUG RESISTANT HIV-1 PROTEASE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1K6T is a [ | 1K6T is a [[Single protein]] structure of sequence from [http://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=1K6T OCA]. | ||
==Reference== | ==Reference== | ||
Lack of synergy for inhibitors targeting a multi-drug-resistant HIV-1 protease., King NM, Melnick L, Prabu-Jeyabalan M, Nalivaika EA, Yang SS, Gao Y, Nie X, Zepp C, Heefner DL, Schiffer CA, Protein Sci. 2002 Feb;11(2):418-29. PMID:[http:// | Lack of synergy for inhibitors targeting a multi-drug-resistant HIV-1 protease., King NM, Melnick L, Prabu-Jeyabalan M, Nalivaika EA, Yang SS, Gao Y, Nie X, Zepp C, Heefner DL, Schiffer CA, Protein Sci. 2002 Feb;11(2):418-29. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11790852 11790852] | ||
[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
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[[Category: inhibitor recognition]] | [[Category: inhibitor recognition]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:13:19 2008'' | ||
Revision as of 13:13, 20 March 2008
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| , resolution 2.25Å | |||||||
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| Ligands: | and | ||||||
| Gene: | POL (Human immunodeficiency virus 1) | ||||||
| Activity: | HIV-1 retropepsin, with EC number 3.4.23.16 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
LACK OF SYNERGY FOR INHIBITORS TARGETING A MULTI-DRUG RESISTANT HIV-1 PROTEASE
OverviewOverview
The three-dimensional structures of indinavir and three newly synthesized indinavir analogs in complex with a multi-drug-resistant variant (L63P, V82T, I84V) of HIV-1 protease were determined to approximately 2.2 A resolution. Two of the three analogs have only a single modification of indinavir, and their binding affinities to the variant HIV-1 protease are enhanced over that of indinavir. However, when both modifications were combined into a single compound, the binding affinity to the protease variant was reduced. On close examination, the structural rearrangements in the protease that occur in the tightest binding inhibitor complex are mutually exclusive with the structural rearrangements seen in the second tightest inhibitor complex. This occurs as adaptations in the S1 pocket of one monomer propagate through the dimer and affect the conformation of the S1 loop near P81 of the other monomer. Therefore, structural rearrangements that occur within the protease when it binds to an inhibitor with a single modification must be accounted for in the design of inhibitors with multiple modifications. This consideration is necessary to develop inhibitors that bind sufficiently tightly to drug-resistant variants of HIV-1 protease to potentially become the next generation of therapeutic agents.
About this StructureAbout this Structure
1K6T is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
ReferenceReference
Lack of synergy for inhibitors targeting a multi-drug-resistant HIV-1 protease., King NM, Melnick L, Prabu-Jeyabalan M, Nalivaika EA, Yang SS, Gao Y, Nie X, Zepp C, Heefner DL, Schiffer CA, Protein Sci. 2002 Feb;11(2):418-29. PMID:11790852
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