Crystal structure of a tethered dimer of HIV-1 proteinase complexed with an inhibitor.
HIV-1 proteinase (HIV PR) is a dimeric enzyme composed of two identical polypeptide chains that associate with twofold symmetry. We have determined to 1.8 A the crystal structure of a covalently tethered dimer of HIV PR. The tethered dimer:inhibitor complex is identical in nearly every respect to the complex of the same inhibitor with the wild type dimeric molecule, except for the linker region. Our results suggest that the tethered dimer may be a useful surrogate enzyme for studying the effects of single site mutations on substrate and inhibitor binding as well as on enzyme asymmetry, and for simulating independent mutational drift of the two domains which has been proposed to have led to the evolution of modern day, single-chain aspartic proteinases.
Bhat
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TN
Structural Biochemistry Program, Frederick Biomedical Supercomputing Center, PRI/DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Baldwin
E T
ET
Liu
B
B
Cheng
Y S
YS
Erickson
J W
JW
D000438:Alcohols / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
C095534:A 76928; D000438:Alcohols; D017320:HIV Protease Inhibitors; D011994:Recombinant Proteins; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease