1lzq
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1lzq |SIZE=350|CAPTION= <scene name='initialview01'>1lzq</scene>, resolution 2.20Å | |PDB= 1lzq |SIZE=350|CAPTION= <scene name='initialview01'>1lzq</scene>, resolution 2.20Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene> | + | |LIGAND= <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=BOC:TERT-BUTYL+HYDROGEN+CARBONATE'>BOC</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PO0:1-BENZYL-(R)-PROPYLAMINE'>PO0</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=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam00077 RVP]</span> | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lzq OCA], [http://www.ebi.ac.uk/pdbsum/1lzq PDBsum], [http://www.fli-leibniz.de/cgi-bin/ImgLib.pl?CODE=1kfv JenaLib], [http://www.rcsb.org/pdb/explore.do?structureId=1lzq RCSB]</span> | ||
}} | }} | ||
| Line 16: | Line 18: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1LZQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ | + | 1LZQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus Human immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LZQ OCA]. |
==Reference== | ==Reference== | ||
An ethylenamine inhibitor binds tightly to both wild type and mutant HIV-1 proteases. Structure and energy study., Skalova T, Hasek J, Dohnalek J, Petrokova H, Buchtelova E, Duskova J, Soucek M, Majer P, Uhlikova T, Konvalinka J, J Med Chem. 2003 Apr 24;46(9):1636-44. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12699382 12699382] | An ethylenamine inhibitor binds tightly to both wild type and mutant HIV-1 proteases. Structure and energy study., Skalova T, Hasek J, Dohnalek J, Petrokova H, Buchtelova E, Duskova J, Soucek M, Majer P, Uhlikova T, Konvalinka J, J Med Chem. 2003 Apr 24;46(9):1636-44. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12699382 12699382] | ||
[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
| - | [[Category: Human immunodeficiency virus | + | [[Category: Human immunodeficiency virus]] |
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Buchtelova, E.]] | [[Category: Buchtelova, E.]] | ||
| Line 32: | Line 34: | ||
[[Category: Soucek, M.]] | [[Category: Soucek, M.]] | ||
[[Category: Uhlikova, T.]] | [[Category: Uhlikova, T.]] | ||
| - | [[Category: BME]] | ||
| - | [[Category: NH2]] | ||
[[Category: ethylenamine isostere]] | [[Category: ethylenamine isostere]] | ||
[[Category: hiv]] | [[Category: hiv]] | ||
| Line 40: | Line 40: | ||
[[Category: protease]] | [[Category: protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 26 05:56:30 2008'' |
Revision as of 03:56, 26 March 2008
| |||||||
| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | HIV-1 retropepsin, with EC number 3.4.23.16 | ||||||
| Domains: | RVP | ||||||
| Resources: | FirstGlance, OCA, PDBsum, JenaLib, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the complex of mutant HIV-1 protease (A71V, V82T, I84V) with an ethylenamine peptidomimetic inhibitor BOC-PHE-PSI[CH2CH2NH]-PHE-GLU-PHE-NH2
Overview
An X-ray structure (resolution 2.2 A) of mutant HIV-1 protease (A71V, V82T, I84V) complexed with a newly developed peptidomimetic inhibitor with an ethylenamine isostere Boc-Phe-Psi[CH(2)CH(2)NH]-Phe-Glu-Phe-NH(2), denoted as OE, is described and compared with the complex of wild-type HIV-1 protease with the same inhibitor (resolution 2.5 A). OE shows tight binding to the wild type (K(i) = 1.5 nM) as well as mutant (K(i) = 4.1 nM) protease. The hydrogen bonds formed, in the case of hydroxyethylamine inhibitors, by a hydroxyl group are, in the case of OE inhibitors, replaced by a bifurcated hydrogen bond from the isosteric NH group to both catalytic aspartates Asp 25 and Asp 125. The binding modes of OE inhibitor to the wild type and mutant protease are similar. However, in the mutant protease, weaker van der Waals interactions of the mutated residues Val 84 and Val 184 with OE were found. This lack of interaction energy is compensated by a new aromatic hydrogen bond between the phenyl ring of the inhibitor in position P1 and the mutated residue Thr 182. Energy analysis based on molecular mechanics has been performed to distinguish between the static and dynamic backgrounds of disorder observed at the mutation sites Thr 82, Val 84, Thr 182, and Val 184.
About this Structure
1LZQ is a Single protein structure of sequence from Human immunodeficiency virus. Full crystallographic information is available from OCA.
Reference
An ethylenamine inhibitor binds tightly to both wild type and mutant HIV-1 proteases. Structure and energy study., Skalova T, Hasek J, Dohnalek J, Petrokova H, Buchtelova E, Duskova J, Soucek M, Majer P, Uhlikova T, Konvalinka J, J Med Chem. 2003 Apr 24;46(9):1636-44. PMID:12699382
Page seeded by OCA on Wed Mar 26 05:56:30 2008
