1daz: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 1daz |SIZE=350|CAPTION= <scene name='initialview01'>1daz</scene>, resolution 1.55Å | |PDB= 1daz |SIZE=350|CAPTION= <scene name='initialview01'>1daz</scene>, resolution 1.55Å | ||
|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=DCL:2-AMINO-4-METHYL-PENTAN-1-OL'>DCL</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1a94|1A94]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1daz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1daz OCA], [http://www.ebi.ac.uk/pdbsum/1daz PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1daz RCSB]</span> | |||
}} | }} | ||
| Line 37: | Line 40: | ||
[[Category: occupancy]] | [[Category: occupancy]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:38:03 2008'' | ||
Revision as of 19:38, 30 March 2008
| |||||||
| , resolution 1.55Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | HIV-1 retropepsin, with EC number 3.4.23.16 | ||||||
| Related: | 1A94
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURAL AND KINETIC ANALYSIS OF DRUG RESISTANT MUTANTS OF HIV-1 PROTEASE
OverviewOverview
Mutants of HIV-1 protease that are commonly selected on exposure to different drugs, V82S, G48V, N88D and L90M, showed reduced catalytic activity compared to the wild-type protease on cleavage site peptides, CA-p2, p6pol-PR and PR-RT, critical for viral maturation. Mutant V82S is the least active (2-20% of wild-type protease), mutants N88D, R8Q, and L90M exhibit activities ranging from 20 to 40% and G48V from 50 to 80% of the wild-type activity. In contrast, D30N is variable in its activity on different substrates (10-110% of wild-type), with the PR-RT site being the most affected. Mutants K45I and M46L, usually selected in combination with other mutations, showed activities that are similar to (60-110%) or greater than (110-530%) wild-type, respectively. No direct relationship was observed between catalytic activity, inhibition, and structural stability. The mutants D30N and V82S were similar to wild-type protease in their stability toward urea denaturation, while R8Q, G48V, and L90M showed 1.5 to 2.7-fold decreased stability, and N88D and K45I showed 1.6 to 1.7-fold increased stability. The crystal structures of R8Q, K45I and L90M mutants complexed with a CA-p2 analog inhibitor were determined at 2.0, 1.55 and 1.88 A resolution, respectively, and compared to the wild-type structure. The intersubunit hydrophobic contacts observed in the crystal structures are in good agreement with the relative structural stability of the mutant proteases. All these results suggest that viral resistance does not arise by a single mechanism.
About this StructureAbout this Structure
1DAZ is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
ReferenceReference
Structural and kinetic analysis of drug resistant mutants of HIV-1 protease., Mahalingam B, Louis JM, Reed CC, Adomat JM, Krouse J, Wang YF, Harrison RW, Weber IT, Eur J Biochem. 1999 Jul;263(1):238-45. PMID:10429209
Page seeded by OCA on Sun Mar 30 19:38:03 2008