PDBsum entry 5ivr

Hydrolase/inhibitor

PDB id: 5ivr

Contents

Protein chains

99 a.a.

Ligands

6EG

Metals

_CL ×4

Waters ×197

PDB id:

5ivr

Name:

Hydrolase/inhibitor

Title:

Crystal structure of HIV protease complexed with methyl n-[(1s)-1-[[2- [(3s)-3-[(4-aminophenyl)methylamino]-4-hydroxy- butyl]phenyl]carbamoyl]-2,2-diphenyl-ethyl]carbamate

Structure:

Protease. Chain: a, b. Engineered: yes

Source:

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

Resolution:

1.50Å R-factor: 0.193 R-free: 0.207

Authors:

H.P.Su

Key ref:

C.J.Bungard et al. (2016). Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group. Acs Med Chem Lett, 7, 702-707. PubMed id: 27437081 DOI: 10.1021/acsmedchemlett.6b00135

Date:

21-Mar-16 Release date: 18-May-16

Protein chains

Q77VV3  (Q77VV3_9HIV1) -  Protease (Fragment) from Human immunodeficiency virus 1

Seq: 99 a.a.

Struc: 99 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1021/acsmedchemlett.6b00135

Acs Med Chem Lett 7:702-707 (2016)

PubMed id: 27437081

Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group.

C.J.Bungard, P.D.Williams, J.E.Ballard, D.J.Bennett, C.Beaulieu, C.Bahnck-Teets, S.S.Carroll, R.K.Chang, D.C.Dubost, J.F.Fay, T.L.Diamond, T.J.Greshock, L.Hao, M.K.Holloway, P.J.Felock, J.J.Gesell, H.P.Su, J.J.Manikowski, D.J.McKay, M.Miller, X.Min, C.Molinaro, O.M.Moradei, P.G.Nantermet, C.Nadeau, R.I.Sanchez, T.Satyanarayana, W.D.Shipe, S.K.Singh, V.L.Truong, S.Vijayasaradhi, C.M.Wiscount, J.P.Vacca, S.N.Crane, J.A.McCauley.

ABSTRACT

A novel HIV protease inhibitor was designed using a morpholine core as the aspartate binding group. Analysis of the crystal structure of the initial lead bound to HIV protease enabled optimization of enzyme potency and antiviral activity. This afforded a series of potent orally bioavailable inhibitors of which MK-8718 was identified as a compound with a favorable overall profile.