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A cumulative specificity model for proteases from human immunodeficiency virus types 1 and 2, inferred from statistical analysis of an extended substrate data base
Statistical analysis of an expanded data base of regions in viral polyproteins and in non-viral proteins that are sensitive to hydrolysis by the protease from human immunodeficiency virus (HIV) type 1 has generated a model which characterizes the substrate specificity of this retroviral enzyme. The...
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| Published in: | The Journal of biological chemistry 1991-08, Vol.266 (22), p.14554-14561 |
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| Main Authors: | , , , |
| Format: | Article |
| Language: | English |
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| cites | cdi_FETCH-LOGICAL-c3553-ce04e8791c22780a5909e4c2b1e72d2fffc083897cc8d10f23d139bb9e1887eb3 |
| container_end_page | 14561 |
| container_issue | 22 |
| container_start_page | 14554 |
| container_title | The Journal of biological chemistry |
| container_volume | 266 |
| creator | POORMAN, R. A TOMASSELLI, A. G HEINRIKSON, R. L KEZDY, F. J |
| description | Statistical analysis of an expanded data base of regions in viral polyproteins and in non-viral proteins that are sensitive
to hydrolysis by the protease from human immunodeficiency virus (HIV) type 1 has generated a model which characterizes the
substrate specificity of this retroviral enzyme. The model leads to an algorithm for predicting protease-susceptible sites
from primary structure. Amino acids in each of the sites from P4 to P4' are tabulated for 40 protein substrates, and the frequency
of occurrence for each residue is compared to the natural abundance of that amino acid in a selected data set of globular
proteins. The results suggest that the highest stringency for particular amino acid residues is at the P2, P1, and P2' positions
of the substrate. The broad specificity of the HIV-1 protease appears to be a consequence of its being able to bind productively
substrates in which interactions with only a few Pi or Pi' side-chains need be optimized. The analysis, extended to 22 protein
segments cleaved by the HIV-2 protease, delineates marked differences in specificity from that of the HIV-1 enzyme. |
| doi_str_mv | 10.1016/S0021-9258(18)98722-3 |
| format | article |
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to hydrolysis by the protease from human immunodeficiency virus (HIV) type 1 has generated a model which characterizes the
substrate specificity of this retroviral enzyme. The model leads to an algorithm for predicting protease-susceptible sites
from primary structure. Amino acids in each of the sites from P4 to P4' are tabulated for 40 protein substrates, and the frequency
of occurrence for each residue is compared to the natural abundance of that amino acid in a selected data set of globular
proteins. The results suggest that the highest stringency for particular amino acid residues is at the P2, P1, and P2' positions
of the substrate. The broad specificity of the HIV-1 protease appears to be a consequence of its being able to bind productively
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to hydrolysis by the protease from human immunodeficiency virus (HIV) type 1 has generated a model which characterizes the
substrate specificity of this retroviral enzyme. The model leads to an algorithm for predicting protease-susceptible sites
from primary structure. Amino acids in each of the sites from P4 to P4' are tabulated for 40 protein substrates, and the frequency
of occurrence for each residue is compared to the natural abundance of that amino acid in a selected data set of globular
proteins. The results suggest that the highest stringency for particular amino acid residues is at the P2, P1, and P2' positions
of the substrate. The broad specificity of the HIV-1 protease appears to be a consequence of its being able to bind productively
substrates in which interactions with only a few Pi or Pi' side-chains need be optimized. The analysis, extended to 22 protein
segments cleaved by the HIV-2 protease, delineates marked differences in specificity from that of the HIV-1 enzyme.</description><subject>Actins - metabolism</subject><subject>AIDS/HIV</subject><subject>Algorithms</subject><subject>Amino Acid Sequence</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Calmodulin - metabolism</subject><subject>Enzymes and enzyme inhibitors</subject><subject>Fundamental and applied biological sciences. 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Psychology</topic><topic>HIV Protease - metabolism</topic><topic>HIV-1 - enzymology</topic><topic>HIV-2 - enzymology</topic><topic>human immunodeficiency virus 2</topic><topic>Hydrolases</topic><topic>Information Systems</topic><topic>inhibitors</topic><topic>Models, Biological</topic><topic>Molecular Sequence Data</topic><topic>proteins</topic><topic>Substrate Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>POORMAN, R. A</creatorcontrib><creatorcontrib>TOMASSELLI, A. G</creatorcontrib><creatorcontrib>HEINRIKSON, R. L</creatorcontrib><creatorcontrib>KEZDY, F. 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to hydrolysis by the protease from human immunodeficiency virus (HIV) type 1 has generated a model which characterizes the
substrate specificity of this retroviral enzyme. The model leads to an algorithm for predicting protease-susceptible sites
from primary structure. Amino acids in each of the sites from P4 to P4' are tabulated for 40 protein substrates, and the frequency
of occurrence for each residue is compared to the natural abundance of that amino acid in a selected data set of globular
proteins. The results suggest that the highest stringency for particular amino acid residues is at the P2, P1, and P2' positions
of the substrate. The broad specificity of the HIV-1 protease appears to be a consequence of its being able to bind productively
substrates in which interactions with only a few Pi or Pi' side-chains need be optimized. The analysis, extended to 22 protein
segments cleaved by the HIV-2 protease, delineates marked differences in specificity from that of the HIV-1 enzyme.</abstract><cop>Bethesda, MD</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>1860861</pmid><doi>10.1016/S0021-9258(18)98722-3</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of biological chemistry, 1991-08, Vol.266 (22), p.14554-14561 |
| issn | 0021-9258 1083-351X |
| language | eng |
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| subjects | Actins - metabolism AIDS/HIV Algorithms Amino Acid Sequence Analytical, structural and metabolic biochemistry Binding Sites Biological and medical sciences Calmodulin - metabolism Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology HIV Protease - metabolism HIV-1 - enzymology HIV-2 - enzymology human immunodeficiency virus 2 Hydrolases Information Systems inhibitors Models, Biological Molecular Sequence Data proteins Substrate Specificity |
| title | A cumulative specificity model for proteases from human immunodeficiency virus types 1 and 2, inferred from statistical analysis of an extended substrate data base |
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