2WPO

HCMV protease inhibitor complex

Summary for 2WPO

• Entry DOI: 10.2210/pdb2wpo/pdb
• Related PRD ID: PRD_000229
• Descriptor: HUMAN CYTOMEGALOVIRUS PROTEASE, (2S)-2-(3,3-dimethylbutanoylamino)-N-[(2S)-1-[[(2S,3S)-3-hydroxy-4-[(4-iodophenyl)methylamino]-4-oxo-butan-2-yl]amino]- 1,4-dioxo-4-pyrrol-1-yl-butan-2-yl]-3,3-dimethyl-butanamide (2 entities in total)
• Functional Keywords: viral protease, hydrolase-hydrolase inhibitor complex, coat protein, serine protease, hydrolase/hydrolase inhibitor
• Biological source: Human herpesvirus 5 (Human cytomegalovirus)
• Cellular location: Protease precursor: Host cytoplasm. Assemblin: Host nucleus. Assembly protein: Host nucleus: P16753
• Total number of polymer chains: 4
• Total formula weight: 115553.16

Authors

Tong, L.,Qian, C.,Massariol, M.-J.,Deziel, R.,Yoakim, C.,Lagace, L. (deposition date: 1998-08-04, release date: 1999-08-04, Last modification date: 2023-08-09)

Primary citation

Tong, L.,Qian, C.,Massariol, M.J.,Deziel, R.,Yoakim, C.,Lagace, L.
Conserved mode of peptidomimetic inhibition and substrate recognition of human cytomegalovirus protease.
Nat.Struct.Biol., 5:819-826, 1998

PubMed Abstract: Human cytomegalovirus (HCMV) protease belongs to a new class of serine proteases, with a unique polypeptide backbone fold. The crystal structure of the protease in complex with a peptidomimetic inhibitor (based on the natural substrates and covering the P4 to P1' positions) has been determined at 2.7 A resolution. The inhibitor is bound in an extended conformation, forming an anti-parallel beta-sheet with the protease. The P3 and P1 side chains are less accessible to solvent, whereas the P4 and P2 side chains are more exposed. The inhibitor binding mode shows significant similarity to those observed for peptidomimetic inhibitors or substrates of other classes of serine proteases (chymotrypsin and subtilisin). HCMV protease therefore represents example of convergent evolution. In addition, large conformational differences relative to the structure of the free enzyme are observed, which may be important for inhibitor binding.

PubMed: 9731777
DOI: 10.1038/1860

Experimental method

X-RAY DIFFRACTION (2.7 Å)