HIV-1 Protease Protein Structures Index

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Tutorials and Museum Exhibits

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A tutorial on HIV-1 Protease structure/function was done by Miyeko Mana and David Marcey from the Online Macromolecular Museum at California Lutheran University.

An Animated GIF Image Movie of Ritonavir (protease inhibotor)Binding to HIV Protease in backbone display mode.
Done with Protein Explorer by Eric Martz. The same animation can be viewed in spacefilled, contacts, or solvent (water) display modes.

The HIV Drug Resistance Database at LANL and the HIV Drug Resistance Database at Stanford are both sources of information on sites in the protease and reverse transcriptase proteins which mutate to create drug resistance in the virus.

A tutorial on HIV protease inhibitor design from the Chemistry department at the University of Wisconsin at Madison.

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PDB Structure Entries

Use the buttons below each entry in the list to get the PubMed entry, protein structure database (PDB) entry, open a Protein Explorer session with the entry, or get the NCBI entry (allowing Cn3D viewing) of the entry.

1ODW:PROTEIN AND PEPTIDE LETTERS 3 pp. 399 (1996). and J Virol. 2003 Mar;77(5):3319-25.

HIV-1 Protease.

1A30: Biochemistry. 1998 Feb 24;37(8):2105-10.

HIV-1 Protease complexed with tripeptide inhibitor from HIV-1 trans-frame region.

1F7A: J Mol Biol 2000 Sep 1;301(5):1207-20.

HIV-1 Protease complexed with peptide substrate and Acetate ions.

1HXW: Proc Natl Acad Sci U S A 1995 Mar 28;92(7):2484-8.

HIV-1 Protease complexed Ritonovir inhibitor 2(C37 H48 N6 O5 S2).

1IZH: J Mol Biol 2000 Sep 1;301(5):1207-20.

HIV-1 Protease complexed with Q50.

1IZI: J Mol Biol 2000 Sep 1;301(5):1207-20.

HIV-1 Protease complexed with Q50 plus a Chloride ion.

1N49: J Mol Biol 2000 Sep 1;301(5):1207-20.

HIV-1 Protease complexed with Ritonovir inhibitor 2(C37 H48 N6 O5 S2).

1KJ4: Structure (Camb). 2002 Mar;10(3):369-81.

HIV-1 Protease inactive variant (D25N) complexed with p17 Matrix|p24 Capsid Cleavage Site Of Hiv-1 Gag (VSQNY|IVQN).

1MT7: J Mol Biol. 2000 Sep 1;301(5):1207-20. Structure (Camb) 2002 Mar;10(3):369-81 Protein Sci. 2002 Feb;11(2):418-29.

HIV-1 Protease complexed with p17 Matrix|p24 Capsid Cleavage Site Of Hiv-1 Gag (VSQNY|IVQN).

1MT8: J Mol Biol. 2000 Sep 1;301(5):1207-20. Structure (Camb) 2002 Mar;10(3):369-81 Protein Sci. 2002 Feb;11(2):418-29.

HIV-1 Protease complexed with Gag p24 Capsid|p2 peptide substrate (KARVL|AEAMS).

1MT9: J Mol Biol. 2000 Sep 1;301(5):1207-20. Structure (Camb) 2002 Mar;10(3):369-81 Protein Sci. 2002 Feb;11(2):418-29.

HIV-1 Protease complexed with P1|P6 Gag Substrate Decapeptide (RPGNF|LQSRP).

1MTB: J Mol Biol. 2000 Sep 1;301(5):1207-20. Structure (Camb) 2002 Mar;10(3):369-81 Protein Sci. 2002 Feb;11(2):418-29.

HIV-1 Protease Complexed With Saquinavir, Ro 31-8959.

1KZK: Biochemistry 2002 Apr 9;41(14):4582-94 J Med Chem 1999 May 20;42(10):1789-802.

HIV-1 Protease Complexed bound to JE-2147 (also named AG1776 or KNI-764; a peptidomimetic protease inhibitor containing a unique unnatural amino acid, allophenylnorstatine [Apns; (2S, 3S)-3-amino-2-hydroxy-4-phenylbutyric acid], with a hydroxymethylcarbonyl (HMC) isostere as the active moiety) at 1.09 A resolution.

1K1T: Proteins 2002 Jul 1;48(1):107-16

HIV-1 Protease K45I/V82S double mutant (Q7K, L33I, L63I, C67A and C95A mutations are also included to stabilize the protein from autoproteolysis, but do not affect drug resistance), complexed with peptide inhibitor RV(Dcl)FEA(Nle) containing 2-AMINO-4-METHYL-PENTAN-1-OL (Dcl) and Norleucine (Nle).

1K1U: Proteins 2002 Jul 1;48(1):107-16

HIV-1 Protease K45I/L90M double mutant (Q7K, L33I, L63I, C67A and C95A mutations are also included to stabilize the protein from autoproteolysis, but do not affect drug resistance), complexed with peptide inhibitor RV(Dcl)FEA(Nle) containing 2-AMINO-4-METHYL-PENTAN-1-OL (Dcl) and Norleucine (Nle).

1K2B: Proteins 2002 Jul 1;48(1):107-16

HIV-1 Protease N88D/L90M double mutant (Q7K, L33I, L63I, C67A and C95A mutations are also included to stabilize the protein from autoproteolysis, but do not affect drug resistance), complexed with peptide inhibitor RV(Dcl)FEA(Nle) containing 2-AMINO-4-METHYL-PENTAN-1-OL (Dcl) and Norleucine (Nle).

1K2C: Proteins 2002 Jul 1;48(1):107-16

HIV-1 Protease D30N/V82S double mutant (Q7K, L33I, L63I, C67A and C95A mutations are also included to stabilize the protein from autoproteolysis, but do not affect drug resistance), complexed with peptide inhibitor RV(Dcl)FEA(Nle) containing 2-AMINO-4-METHYL-PENTAN-1-OL (Dcl) and Norleucine (Nle).

1DAZ: Eur J Biochem 1999 Jul;263(1):238-45.

HIV-1 Protease mutant K45I complexed with peptide inhibitor RV(Dcl)FEA(Nle) containing 2-AMINO-4-METHYL-PENTAN-1-OL (Dcl) and Norleucine (Nle).

1DW6: Eur J Biochem 1999 Jul;263(1):238-45.

HIV-1 Protease mutant L90M complexed with peptide inhibitor RV(Dcl)FEA(Nle) containing 2-AMINO-4-METHYL-PENTAN-1-OL (Dcl) and Norleucine (Nle).

1EBK: Eur J Biochem 1999 Jul;263(1):238-45.

HIV-1 Protease mutant R8Q complexed with peptide inhibitor RV(Dcl)FEA(Nle) containing 2-AMINO-4-METHYL-PENTAN-1-OL (Dcl) and Norleucine (Nle).

1DIF: Adv Exp Med Biol. 1995;362:451-4. J Mol Biol. 1996 Jan 19;255(2):321-46.

HIV-1 protease in complex with a pseudo-C2 symmetric inhibitor, (A79285) which contains a central difluoroketone motif.

1MTR: Biochemistry 1999 Jun 22;38(25):7978-88.

HIV-1 protease complexed with a cyclic Phe-Ile-Val Peptidomimetic Inhibitor.

1B6L: Biochemistry 1999 Jun 22;38(25):7978-88.

HIV-1 protease complexed with PI4 {1-[2-(8-CARBAMOYLMETHYL-6,9- DIOXO-2-OXA-7,10-DIAZA-BICYCLO[11.2.2]HEPTADECA- 1( 16),13(17),14- TRIEN-11-YL)-2-HYDROXY-ETHYL]-PIPERIDINE-2-CARBOXYLIC ACID TERT- BUTYLAMIDE}.

1B6N: Biochemistry 1999 Jun 22;38(25):7978-88.

HIV-1 protease complexed with PI3 {11-[1-HYDROXY-2-(3-METHYL- BUTYLAMINO)-ETHYL]-8-ISOPROPYL-2-OXA-7,10- DIAZA- BICYCLO[11.2.2] HEPTADECA-1(16),13(17),14-TRIENE-6,9-DIONE}

1B6K: Biochemistry 1999 Jun 22;38(25):7978-88.

HIV-1 protease complexed with PI5 {N-[3-(8-SEC-BUTYL-7,10-DIOXO-2- OXA-6,9-DIAZA-BICYCLO[11.2.2]HEPTADECA-1(16),13( 17),14-TRIEN-11- YLAMINO)-2-HYDROXY-1-(4-HYDROXY-BENZYL)-PROPYL]-3-METHYL-2- ( 2-OXO- PYRROLIDIN-1-YL)-BUTYRAMIDE}.

1B6P: Biochemistry 1999 Jun 22;38(25):7978-88.

HIV-1 protease complexed with PI7 {N-[3-(8-SEC-BUTYL-7,10-DIOXO-2- OXA-6,9-DIAZA-BICYCLO[11.2.2] HEPTADECA-1(16), 13(17),14-TRIEN-11- YAMINO)-2-HYDROXY-1-(4-HYDROXY-BENZYL) -PROPYL]-3-METHYL-2- PROPIONYLAMINO-BUTYRAMIDE}.

1B6M: Biochemistry 1999 Jun 22;38(25):7978-88.

HIV-1 protease complexed with PI6 {[1-BENZYL-3-(8-SEC-BUTYL-7, 10-DIOXO-2-OXA-6,9-DIAZA-BICYCLO[11.2.2] HEPTADECA- 1(16),13(17), 14-TRIEN-11-YLAMINO)-2-HYDROXY-PROPYL] -CARBAMIC ACID TERT-BUTYL ESTER}.

1B6J: Biochemistry 1999 Jun 22;38(25):7978-88.

HIV-1 protease complexed with PI1 {1-[2-(8-CARBAMOYLMETHYL-6,9- DIOXO-2-OXA-7,10-DIAZA-BICYCLO[11.2.2] HEPTADECA-1( 16),13(17), 14-TRIEN-11-YL)-2-HYDROXY-ETHYL] -PYRROLIDINE-2-CARBOXYLIC ACID [1-( 1-CARBAMOYL-2-METHYL-PROPYLCARBAMOYL) -2-METHYL-BUTYL]-AMIDE}.

1JLD: J Med Chem 1997 Jul 4;40(14):2164-76.

HIV-2 protease complexed with {3-(CARBOXYAMIDE(2-CARBOXYAMIDE- 2-TERTBUTYLETHYL))PENTAN} inhibitor.

1B6O: Biochemistry 1999 Jun 22;38(25):7978-88.

HIV-1 protease complexed with PI2 {2-{11-[1-HYDROXY-2- (3-METHYL-BUTYLAMINO)-ETHYL] -6,9-DIOXO-2-OXA-7,10-DIAZA- BICYCLO [11.2.2]HEPTADECA-1(16),13(17),14-TRIEN-8-YL}-ACETAMIDE)}.

1D4K: Biochemistry 1999 Jun 22;38(25):7978-88.

HIV-1 protease complexed with PI8 {N-13-[(10S,13S)-9,12-DIOXO-10- (2-BUTYL)-2-OXA-8,11-DIAZABICYCLO [13.2.2] NONADECA-15,17,18-TRIENE] (2R)-BENZYL-(4S)-HYDROXY-5-AMINOPENTANOIC (1R)-HYDROXY-(2S -INDANEAMIDE}.

1D4L: Biochemistry 1999 Jun 22;38(25):7978-88.

HIV-1 protease complexed with PI2 {(10S,13S,1"R)-13-[1"-HYDROXY-2"- (N-P-AMINOBENZENESULFONYL-1""-AMINO-3""-METHYLBUTYL)ETHYL] 8,11-DIOXO- 10-ISOPROPYL-2-OXA-9,12-DIAZABICYCLO [13.2.2]NONADECA-15,17,18-TRIENE}.

1QBR: J Med Chem. 1997 Jan 17;40(2):181-91.

HIV-1 protease complexed with a cyclic urea amide inhibitor {[4R-(4ALPHA,5ALPHA,6BETA,7BETA)] -3,3'-[[TETRAHYDRO-5,6-DIHYDROXY-2-OXO-4,7-BIS( PHENYLMETHYL)- 1H-1,3-DIAZEPINE-1,3(2H)-DIYL]BIS(METHYLENE)]BIS[N-2-THIAZOLYLBENZAMIDE]}.

1G35: J Med Chem 2001 Jan 18;44(2):155-69.

Hiv-1 protease complexed with inhibitor, AHA024 {2-[4-(HYDROXY- METHOXY-METHYL)-BENZYL]-7-(4-HYDROXYMETHYL-BENZYL)-1,1-DIOXO-3,6- BIS-PHENOXYMETHYL 1LAMBDA6-[1,2,7]THIADIAZEPANE-4,5-DIOL}.

1G2K: J Med Chem 2001 Jan 18;44(2):155-69.

Hiv-1 protease complexed with inhibitor, AHA047 {3-(7-BENZYL-4,5- DIHYDROXY-1,1-DIOXO-3,6-BIS-PHENOXYMETHYL-1L6-[1,2,7]THIADIAZEPAN-2- YLMETHYL)-N-METHYL-BENZAMIDE}.

1EBW: Bioorg Med Chem 2003 Mar 20;11(6):1107-15

Hiv-1 protease complexed with inhibitor, BEA322 {N,N-[2,5-O-[DIBENZYL] -GLUCARYL]-DI-[ISOLEUCYL-AMIDO-METHANE]}.

1ODY: Protein Sci. 1998 Nov;7(11):2314-23.

HIV-1 Protease Complexed with statine-based inhibitor Lp-130 (ACE-NAL-VAL-STA-ABU-NAL-NH2) where NAL is Naphthylalanine, STA is Statine, and ABU is 2-Aminobutyric Acid.

4FIV: Protein Sci. 1998 Nov;7(11):2314-23.

FIV (Feline Immunodeficiency Virus) Protease Complexed with statine-based inhibitor Lp-130 (ACE-NAL-VAL-STA-ABU-NAL-NH2) where NAL is Naphthylalanine, STA is Statine, and ABU is 2-Aminobutyric Acid.

2FMB: Protein Sci. 1998 Nov;7(11):2314-23.

EIAV (Equine Infectious Anemia Virus) Protease Complexed with statine-based inhibitor Lp-130 (ACE-NAL-VAL-STA-ABU-NAL-NH2) where NAL is Naphthylalanine, STA is Statine, and ABU is 2-Aminobutyric Acid.

1NSO: J Mol Biol. 2003 Oct 31;333(4):771-80.

Mason-Pfizer Monkey Virus Protease (D26N/C7A/C106A triple mutant) Monomer.

Other HIV-1 Protease Entries at SCOP (Structural Classification of Proteins) server.

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Publications on Protease Structures

The application of structure-based drug design to members of the aspartic proteinase family. Review
Cooper JB.
Aspartic proteinases in disease: a structural perspective.
Curr Drug Targets. 2002 Apr;3(2):155-73.
PMID: 11958298

Exploration of Fullerene C(60) Potential to Bind in Protease
Zhu Z, Schuster DI, Tuckerman ME.
Molecular dynamics study of the connection between flap closing and binding of fullerene-based inhibitors of the HIV-1 protease.
Biochemistry 2003 Feb 11;42(5):1326-33.
PMID: 12564936

HIV-1 Protease inactive drug-resistant mutant (D25N/V82A).
Prabu-Jeyabalan M, Nalivaika EA, King NM, Schiffer CA.
Viability of a drug-resistant human immunodeficiency virus type 1 protease variant: structural insights for better antiviral therapy.
J Virol. 2003 Jan;77(2):1306-15.
PMID: 12502847

A comparison of the Mason-Pfizer Monkey Virus protease to HIV-1 Protease.
Veverka V, Bauerova H, Zabransky A, Lang J, Ruml T, Pichova I, Hrabal R.
Three-dimensional structure of a monomeric form of a retroviral protease.
J Mol Biol. 2003 Oct 31;333(4):771-80.
PMID: 14568536

The HIV-1 Protease pseudopeptide inhibitor, QF34.
Weber J, Mesters JR, Lepsik M, Prejdova J, Svec M, Sponarova J, Mlcochova P, Skalicka K, Strisovsky K, Uhlikova T, Soucek M, Machala L, Stankova M, Vondrasek J, Klimkait T, Kraeusslich HG, Hilgenfeld R, Konvalinka J.
Unusual binding mode of an HIV-1 protease inhibitor explains its potency against multi-drug-resistant virus strains.
J Mol Biol. 2002 Dec 6;324(4):739-54.
PMID: 12460574

HIVdb: a database of the structures of human immunodeficiency virus protease.
Vondrasek J, Wlodawer A.
HIVdb: a database of the structures of human immunodeficiency virus protease.
Proteins. 2002 Dec 1;49(4):429-31.
PMID: 12402352

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Databases of HIV-1 Protease Structures

The HIV-1 Protease Structures Database at the National Institute of Standards and Technology (NIST) contains many protease structures which have not been submitted to the PDB. The structures from this database can be viewed as Kinemages, but not other formats such as PDB.

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