5OIN

InhA (T2A mutant) complexed with N-(1-(pyrimidin-2-yl)piperidin-4-yl)acetamide

Summary for 5OIN

• Entry DOI: 10.2210/pdb5oin/pdb
• Descriptor: Enoyl-[acyl-carrier-protein] reductase [NADH], NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ~{N}-(1-pyrimidin-2-ylpiperidin-4-yl)ethanamide, ... (4 entities in total)
• Functional Keywords: inhibitor, complex, fragment based drug discovery, tuberculosis, oxidoreductase
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 4
• Total formula weight: 117413.53

Authors

Convery, M.A. (deposition date: 2017-07-19, release date: 2018-02-14, Last modification date: 2024-05-08)

Primary citation

Prati, F.,Zuccotto, F.,Fletcher, D.,Convery, M.A.,Fernandez-Menendez, R.,Bates, R.,Encinas, L.,Zeng, J.,Chung, C.W.,De Dios Anton, P.,Mendoza-Losana, A.,Mackenzie, C.,Green, S.R.,Huggett, M.,Barros, D.,Wyatt, P.G.,Ray, P.C.
Screening of a Novel Fragment Library with Functional Complexity against Mycobacterium tuberculosis InhA.
ChemMedChem, 13:672-677, 2018

PubMed 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.

PubMed: 29399991
DOI: 10.1002/cmdc.201700774

Experimental method

X-RAY DIFFRACTION (2.82 Å)