PDBsum entry 5oip

Oxidoreductase

PDB id: 5oip

Contents

Protein chain

268 a.a.

Ligands

NAD

9WE

PO4

Waters ×304

PDB id:

5oip

Name:

Oxidoreductase

Title:

Inha (t2a mutant) complexed with 1-(pyridin-3-ylmethyl)-3-(1- (pyrimidin-2-yl)piperidin-4-yl)urea

Structure:

Enoyl-[acyl-carrier-protein] reductase [nadh]. Chain: a. Synonym: enoyl-acp reductase,fas-ii enoyl-acp reductase,nadh- dependent 2-trans-enoyl-acp reductase. Engineered: yes. Mutation: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 83332. Strain: atcc 25618 / h37rv. Gene: inha, rv1484, mtcy277.05. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.71Å R-factor: 0.161 R-free: 0.173

Authors:

M.A.Convery

Key ref:

F.Prati et al. (2018). Screening of a Novel Fragment Library with Functional Complexity against Mycobacterium tuberculosis InhA. ChemMedChem, 13, 672-677. PubMed id: 29399991 DOI: 10.1002/cmdc.201700774

Date:

19-Jul-17 Release date: 14-Feb-18

Protein chain

P9WGR1  (INHA_MYCTU) -  Enoyl-[acyl-carrier-protein] reductase [NADH] from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Seq: 269 a.a.

Struc: 268 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.1.3.1.9 - enoyl-[acyl-carrier-protein] reductase (NADH).
• Reaction: a 2,3-saturated acyl-[ACP] + NAD⁺ = a (2E)-enoyl-[ACP] + NADH + H⁺

2,3-saturated acyl-[ACP] + NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly) = (2E)-enoyl-[ACP] + NADH + H(+)

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

Added reference

DOI no: 10.1002/cmdc.201700774

ChemMedChem 13:672-677 (2018)

PubMed id: 29399991

Screening of a Novel Fragment Library with Functional Complexity against Mycobacterium tuberculosis InhA.

F.Prati, F.Zuccotto, D.Fletcher, M.A.Convery, R.Fernandez-Menendez, R.Bates, L.Encinas, J.Zeng, C.W.Chung, P.De Dios Anton, A.Mendoza-Losana, C.Mackenzie, S.R.Green, M.Huggett, D.Barros, P.G.Wyatt, P.C.Ray.

ABSTRACT

Our findings reported herein provide support for the benefits of including functional group complexity (FGC) within fragments when screening against protein targets such as Mycobacterium tuberculosis InhA. We show that InhA fragment actives with FGC maintained their binding pose during elaboration. Furthermore, weak fragment hits with functional group handles also allowed for facile fragment elaboration to afford novel and potent InhA inhibitors with good ligand efficiency metrics for optimization.