3SLZ

The crystal structure of XMRV protease complexed with TL-3

Summary for 3SLZ

• Entry DOI: 10.2210/pdb3slz/pdb
• Related: 3NR6 3SM1 3SM2
• Related PRD ID: PRD_000434
• Descriptor: gag-pro-pol polyprotein, benzyl [(1S,4S,7S,8R,9R,10S,13S,16S)-7,10-dibenzyl-8,9-dihydroxy-1,16-dimethyl-4,13-bis(1-methylethyl)-2,5,12,15,18-pentaoxo-20-phenyl-19-oxa-3,6,11,14,17-pentaazaicos-1-yl]carbamate, FORMIC ACID, ... (5 entities in total)
• Functional Keywords: beta sheet and dimer, protease, peptide inhibitor, tl-3 pepstatina, virus, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: DG-75 Murine leukemia virus
• Total number of polymer chains: 2
• Total formula weight: 29898.80

Authors

Li, M.,Gustchina, A.,Wlodawer, A. (deposition date: 2011-06-27, release date: 2011-10-12, Last modification date: 2024-02-28)

Primary citation

Li, M.,Gustchina, A.,Matuz, K.,Tozser, J.,Namwong, S.,Goldfarb, N.E.,Dunn, B.M.,Wlodawer, A.
Structural and biochemical characterization of the inhibitor complexes of xenotropic murine leukemia virus-related virus protease.
Febs J., 278:4413-4424, 2011

PubMed Abstract: Interactions between the protease (PR) encoded by the xenotropic murine leukemia virus-related virus and a number of potential inhibitors have been investigated by biochemical and structural techniques. It was observed that several inhibitors used clinically against HIV PR exhibit nanomolar or even subnanomolar values of K(i) , depending on the exact experimental conditions. Both TL-3, a universal inhibitor of retroviral PRs, and some inhibitors originally shown to inhibit plasmepsins were also quite potent, whereas inhibition by pepstatin A was considerably weaker. Crystal structures of the complexes of xenotropic murine leukemia virus-related virus PR with TL-3, amprenavir and pepstatin A were solved at high resolution and compared with the structures of complexes of these inhibitors with other retropepsins. Whereas TL-3 and amprenavir bound in a predictable manner, spanning the substrate-binding site of the enzyme, two molecules of pepstatin A bound simultaneously in an unprecedented manner, leaving the catalytic water molecule in place.

PubMed: 21951660
DOI: 10.1111/j.1742-4658.2011.08364.x

Experimental method

X-RAY DIFFRACTION (1.4 Å)