Summary for peptidase A02.001: HIV-1 retropepsin

Summary Alignment Sequences Sequence features Distribution Structure Literature Substrates Inhibitors Pharma

 

Names
MEROPS NameHIV-1 retropepsin
Other namesHIV-1 protease, retropepsin (human immunodeficiency virus 1)
Domain architecture
MEROPS Classification
Classification Clan AA >> Subclan (none) >> Family A2 >> Subfamily A >> A02.001
HolotypeHIV-1 retropepsin (human immunodeficiency virus 1), Uniprot accession P04586 (peptidase unit: 504-599), MERNUM MER0001449
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeAspartic
PeplistIncluded in the Peplist with identifier PL00025
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.23 (Aspartic endopeptidases) >> Peptidase 3.4.23.16
EnzymologyBRENDA database
ActivityHIV-1 retropepsin cleaves the gag-pol polyprotein at eight sites, mostly with hydrophobic residues in P1 and P1’ (reviewed by <%Dunn & Rao, 2004[20040525A175]%>).
Proteolytic eventsCutDB database (26 cleavages)
InhibitorsIn addition to the conventional inhibitors there are experimental compounds that interfere with the dimerization that is necessary to form the active peptidase (Lee & Chmielewski, 2006).
StructureThe peptidase contains only beta secondary structural elements. Retropepsins are active only as their homodimers.
PhysiologyProcessing of viral polyprotein of human immunodeficiency virus type 1. Also cleavage of host cell proteins.
Pharmaceutical relevanceHIV-1 retropepsin is an important drug target for human immunodeficiency virus infection (Wlodawer & Vondrasek, 1998).
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/HIV-1_protease
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/ve/lScissile bondl/eva/-/- (based on 1045 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 82 95 18 55 17 7 43 74
Pro 125 11 0 1 99 4 3 68
Ala 111 109 97 58 121 149 116 83
Val 29 44 272 8 130 188 99 48
Leu 39 104 33 263 224 84 114 80
Ile 18 24 93 7 82 125 62 52
Met 17 21 11 72 43 10 95 52
Phe 11 68 4 156 122 9 65 22
Tyr 16 19 8 154 66 1 29 2
Trp 3 21 1 22 8 1 7 7
Ser 172 34 15 63 22 24 59 92
Thr 60 32 49 0 49 58 42 132
Cys 14 21 10 17 3 10 9 5
Asn 24 17 108 31 6 13 26 43
Gln 24 98 8 14 7 76 71 82
Asp 56 66 80 59 10 20 86 84
Glu 77 79 194 58 21 263 50 61
Lys 8 33 0 0 2 1 16 15
Arg 14 68 1 2 8 0 18 23
His 15 19 6 5 4 2 35 18