PDBsum entry 2zye

Hydrolase/hydrolase inhibitor

PDB id: 2zye

Contents

Protein chains

99 a.a. *

Ligands

KNI

DOD ×93

Waters ×50

* Residue conservation analysis

PDB id:

2zye

Name:

Hydrolase/hydrolase inhibitor

Title:

Structure of HIV-1 protease in complex with potent inhibitor kni-272 determined by neutron crystallography

Structure:

Protease. Chain: a, b. Engineered: yes. Mutation: yes

Source:

Human immunodeficiency virus 1. Organism_taxid: 11676. Gene: pol. Expressed in: escherichia coli. Expression_system_taxid: 562.

Authors:

M.Adachi,T.Ohhara,T.Tamada,N.Okazaki,R.Kuroki

Key ref:

M.Adachi et al. (2009). Structure of HIV-1 protease in complex with potent inhibitor KNI-272 determined by high-resolution X-ray and neutron crystallography. Proc Natl Acad Sci U S A, 106, 4641-4646. PubMed id: 19273847 DOI: 10.1073/pnas.0809400106

Date:

20-Jan-09 Release date: 24-Mar-09

Protein chains

P03367  (POL_HV1BR) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI)

Seq: 1447 a.a.

Struc: 99 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.2.7.7.- - ?????
• Enzyme class 2: E.C.2.7.7.49 - RNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 3: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 4: E.C.3.1.-.-
• Enzyme class 5: E.C.3.1.13.2 - exoribonuclease H.
• Reaction: Exonucleolytic cleavage to 5'-phosphomonoester oligonucleotides in both 5'- to 3'- and 3'- to 5'-directions.
• Enzyme class 6: E.C.3.1.26.13 - retroviral ribonuclease H.
• Enzyme class 7: E.C.3.4.23.16 - HIV-1 retropepsin.
• Reaction: Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1073/pnas.0809400106

Proc Natl Acad Sci U S A 106:4641-4646 (2009)

PubMed id: 19273847

Structure of HIV-1 protease in complex with potent inhibitor KNI-272 determined by high-resolution X-ray and neutron crystallography.

M.Adachi, T.Ohhara, K.Kurihara, T.Tamada, E.Honjo, N.Okazaki, S.Arai, Y.Shoyama, K.Kimura, H.Matsumura, S.Sugiyama, H.Adachi, K.Takano, Y.Mori, K.Hidaka, T.Kimura, Y.Hayashi, Y.Kiso, R.Kuroki.

ABSTRACT

HIV-1 protease is a dimeric aspartic protease that plays an essential role in viral replication. To further understand the catalytic mechanism and inhibitor recognition of HIV-1 protease, we need to determine the locations of key hydrogen atoms in the catalytic aspartates Asp-25 and Asp-125. The structure of HIV-1 protease in complex with transition-state analog KNI-272 was determined by combined neutron crystallography at 1.9-A resolution and X-ray crystallography at 1.4-A resolution. The resulting structural data show that the catalytic residue Asp-25 is protonated and that Asp-125 (the catalytic residue from the corresponding diad-related molecule) is deprotonated. The proton on Asp-25 makes a hydrogen bond with the carbonyl group of the allophenylnorstatine (Apns) group in KNI-272. The deprotonated Asp-125 bonds to the hydroxyl proton of Apns. The results provide direct experimental evidence for proposed aspects of the catalytic mechanism of HIV-1 protease and can therefore contribute substantially to the development of specific inhibitors for therapeutic application.

Selected figure(s)

Figure 1.
Tertiary structure of HIV-1 protease determined by neutron diffraction. The HIV protease dimer is shown by a ball and stick model; water molecules and bound inhibitor are shown by space-filling representation. Hydrogen and deuterium atoms are colored gray. Carbon (green), oxygen (red), nitrogen (blue), and sulfur (yellow) atoms in protease are indicated. Carbon atoms in KNI-272 are colored dark gray. Figs. 1, 2, and 4 were made by using the program Pymol (www.pymol.org).

Figure 3.
Schematic diagram of the interaction between HIV-1 protease and KNI-272 (bold lines). Hydrogen bonds are shown by broken lines. Asterisks indicate the hydrogen atoms replaced with deuterium atom (occupancies of deuterium atom are >0.5).

Figures were selected by an automated process.