PDBsum entry 5e5j

Hydrolase/hydrolase inhibitor

PDB id: 5e5j

Contents

Protein chains

99 a.a.

Ligands

017

DOD ×116

PDB id:

5e5j

Name:

Hydrolase/hydrolase inhibitor

Title:

Joint x-ray/neutron structure of HIV-1 protease triple mutant (v32i, i47v,v82i) with darunavir at ph 6.0

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

Resolution:

1.85Å R-factor: 0.194 R-free: 0.201

Authors:

A.Y.Kovalevsky,O.O.Gerlits

Key ref:

O.Gerlits et al. (2016). Long-Range Electrostatics-Induced Two-Proton Transfer Captured by Neutron Crystallography in an Enzyme Catalytic Site. Angew Chem Int Ed Engl, 55, 4924-4927. PubMed id: 26958828 DOI: 10.1002/anie.201509989

Date:

08-Oct-15 Release date: 04-May-16

Protein chains

Q7SSI0  (Q7SSI0_9HIV1) -  Protease (Fragment) from Human immunodeficiency virus 1

Seq: 99 a.a.

Struc: 99 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1002/anie.201509989

Angew Chem Int Ed Engl 55:4924-4927 (2016)

PubMed id: 26958828

Long-Range Electrostatics-Induced Two-Proton Transfer Captured by Neutron Crystallography in an Enzyme Catalytic Site.

O.Gerlits, T.Wymore, A.Das, C.H.Shen, J.M.Parks, J.C.Smith, K.L.Weiss, D.A.Keen, M.P.Blakeley, J.M.Louis, P.Langan, I.T.Weber, A.Kovalevsky.

ABSTRACT

Neutron crystallography was used to directly locate two protons before and after a pH-induced two-proton transfer between catalytic aspartic acid residues and the hydroxy group of the bound clinical drug darunavir, located in the catalytic site of enzyme HIV-1 protease. The two-proton transfer is triggered by electrostatic effects arising from protonation state changes of surface residues far from the active site. The mechanism and pH effect are supported by quantum mechanics/molecular mechanics (QM/MM) calculations. The low-pH proton configuration in the catalytic site is deemed critical for the catalytic action of this enzyme and may apply more generally to other aspartic proteases. Neutrons therefore represent a superb probe to obtain structural details for proton transfer reactions in biological systems at a truly atomic level.