3K4V

New crystal form of HIV-1 Protease/Saquinavir structure reveals carbamylation of N-terminal proline

Summary for 3K4V

• Entry DOI: 10.2210/pdb3k4v/pdb
• Related PRD ID: PRD_000454
• Descriptor: HIV-1 Protease, DIMETHYL SULFOXIDE, (2S)-N-[(2S,3R)-4-[(2S,3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-hydroxy-1 -phenyl-butan-2-yl]-2-(quinolin-2-ylcarbonylamino)butanediamide, ... (6 entities in total)
• Functional Keywords: hydrolase-hydrolase inhibitor complex, carbamylation, aids, aspartyl protease, capsid maturation, capsid protein, hydrolase/hydrolase inhibitor
• Biological source: Human immunodeficiency virus type 1 (HIV-1); More
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P03366 P03366
• Total number of polymer chains: 4
• Total formula weight: 44706.43

Authors

Olajuyigbe, F.M.,Demitri, N.,Ajele, J.O.,Maurizio, E.,Randaccio, L.,Geremia, S. (deposition date: 2009-10-06, release date: 2010-06-09, Last modification date: 2023-09-06)

Primary citation

Olajuyigbe, F.M.,Demitri, N.,Ajele, J.O.,Maurizio, E.,Randaccio, L.,Geremia, S.
Carbamylation of N-terminal proline.
ACS Med Chem Lett, 1:254-257, 2010

PubMed Abstract: Protein carbamylation is of great concern both in vivo and in vitro. Here, we report the first structural characterization of a protein carbamylated at the N-terminal proline. The unexpected carbamylation of the α-amino group of the least reactive codified amino acid has been detected in high-resolution electron density maps of a new crystal form of the HIV-1 protease/saquinavir complex. The carbamyl group is found coplanar to the proline ring with a trans conformation. The reaction of N-terminal with cyanate ion derived from the chaotropic agent urea was confirmed by mass spectra analysis on protease single crystals. Implications of carbamylation process in vitro and in vivo are discussed.

PubMed: 24900204
DOI: 10.1021/ml100046d

Experimental method

X-RAY DIFFRACTION (1.39 Å)