PDBsum entry 4l1a

Hydrolase/hydrolase inhibitor

PDB id: 4l1a

Contents

Protein chains

99 a.a.

99 a.a.

Ligands

AB1

Waters ×222

PDB id:

4l1a

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystallographic study of multi-drug resistant HIV-1 protease lopinavir complex: mechanism of drug recognition and resistance

Structure:

Mdr769 HIV-1 protease. Chain: a. Engineered: yes. Mdr769 HIV-1 protease. Chain: b. Engineered: yes

Source:

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

Resolution:

1.90Å R-factor: 0.201 R-free: 0.260

Authors:

Z.Liu,R.S.Yedidi,Y.Wang,T.Dewdney,S.Reiter,J.Brunzelle,I.Kovari, L.Kovari

Key ref:

Z.Liu et al. (2013). Crystallographic study of multi-drug resistant HIV-1 protease lopinavir complex: mechanism of drug recognition and resistance. Biochem Biophys Res Commun, 437, 199-204. PubMed id: 23792096 DOI: 10.1016/j.bbrc.2013.06.027

Date:

03-Jun-13 Release date: 02-Apr-14

Protein chain

Q000H7  (Q000H7_9HIV1) -  Pol protein (Fragment) from Human immunodeficiency virus 1

Seq: 404 a.a.

Struc: 99 a.a.*

Protein chain

Q000H7  (Q000H7_9HIV1) -  Pol protein (Fragment) from Human immunodeficiency virus 1

Seq: 404 a.a.

Struc: 99 a.a.*

* PDB and UniProt seqs differ at 9 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.1.26.13 - retroviral ribonuclease H.

DOI no: 10.1016/j.bbrc.2013.06.027

Biochem Biophys Res Commun 437:199-204 (2013)

PubMed id: 23792096

Crystallographic study of multi-drug resistant HIV-1 protease lopinavir complex: mechanism of drug recognition and resistance.

Z.Liu, R.S.Yedidi, Y.Wang, T.G.Dewdney, S.J.Reiter, J.S.Brunzelle, I.A.Kovari, L.C.Kovari.

ABSTRACT

Lopinavir (LPV) is a second generation HIV-1 protease inhibitor. Drug resistance has rapidly emerged against LPV since its US FDA approval on September 15, 2000. Mutations at residues 32I, L33F, 46I, 47A, I54V, V82A, I84V, and L90M render the protease drug resistant against LPV. We report the crystal structure of a clinical isolate multi-drug resistant (MDR) 769 HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, and 90) complexed with LPV and the in vitro enzymatic IC50 of LPV against MDR 769. The structural and functional studies demonstrate significant drug resistance of MDR 769 against LPV, arising from reduced interactions between LPV and the protease target.