PDBsum entry 3c6u

Transferase

PDB id: 3c6u

Contents

Protein chains

558 a.a. *

404 a.a. *

Ligands

M22

Waters ×375

* Residue conservation analysis

PDB id:

3c6u

Name:

Transferase

Title:

Crystal structure of HIV reverse transcriptase in complex with inhibitor 22

Structure:

Reverse transcriptase. Chain: a. Synonym: p66 rt. Engineered: yes. Reverse transcriptase. Chain: b. Synonym: p51 rt. Engineered: yes

Source:

HIV-1 m:b_hxb2r. Organism_taxid: 11706. Strain: hxb2 isolate. Gene: gag-pol. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562

Resolution:

2.70Å R-factor: 0.198 R-free: 0.275

Authors:

Y.Yan,S.Prasad

Key ref:

T.J.Tucker et al. (2008). The design and synthesis of diaryl ether second generation HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with enhanced potency versus key clinical mutations. Bioorg Med Chem Lett, 18, 2959-2966. PubMed id: 18396399 DOI: 10.1016/j.bmcl.2008.03.064

Date:

05-Feb-08 Release date: 22-Apr-08

Protein chain

P04585  (POL_HV1H2) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)

Seq: 1435 a.a.

Struc: 558 a.a.*

Protein chain

P04585  (POL_HV1H2) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)

Seq: 1435 a.a.

Struc: 404 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: Chains A, B: E.C.2.7.7.- - ?????
• Enzyme class 2: Chains A, B: 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: Chains A, B: 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: Chains A, B: E.C.3.1.-.-
• Enzyme class 5: Chains A, B: 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: Chains A, B: E.C.3.1.26.13 - retroviral ribonuclease H.
• Enzyme class 7: Chains A, B: 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: 10.1016/j.bmcl.2008.03.064

Bioorg Med Chem Lett 18:2959-2966 (2008)

PubMed id: 18396399

The design and synthesis of diaryl ether second generation HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with enhanced potency versus key clinical mutations.

T.J.Tucker, S.Saggar, J.T.Sisko, R.M.Tynebor, T.M.Williams, P.J.Felock, J.A.Flynn, M.T.Lai, Y.Liang, G.McGaughey, M.Liu, M.Miller, G.Moyer, V.Munshi, R.Perlow-Poehnelt, S.Prasad, R.Sanchez, M.Torrent, J.P.Vacca, B.L.Wan, Y.Yan.

ABSTRACT

Using a combination of traditional Medicinal Chemistry/SAR analysis, crystallography, and molecular modeling, we have designed and synthesized a series of novel, highly potent NNRTIs that possess broad antiviral activity against a number of key clinical mutations.