PDBsum entry 6pg2

Oxidoreductase/inhibitor

PDB id: 6pg2

Contents

Protein chains

188 a.a.

Ligands

O6Y

Metals

_CU

Waters ×295

PDB id:

6pg2

Name:

Oxidoreductase/inhibitor

Title:

Crystal structure of ecdsba in a complex with unpurified reaction product h5 (morpholine 8)

Structure:

Thiol:disulfide interchange protein dsba. Chain: a, b. Engineered: yes

Source:

Escherichia coli (strain k12). Organism_taxid: 83333. Strain: k12. Gene: dsba, dsf, ppfa, b3860, jw3832. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.91Å R-factor: 0.186 R-free: 0.223

Authors:

O.V.Ilyichova,M.Bentley,B.Doak,M.J.Scanlon

Key ref:

M.R.Bentley et al. (2020). Rapid Elaboration of Fragments into Leads by X-ray Crystallographic Screening of Parallel Chemical Libraries (REFiL_X). J Med Chem, 63, 6863-6875. PubMed id: 32529824 DOI: 10.1021/acs.jmedchem.0c00111

Date:

23-Jun-19 Release date: 06-May-20

Protein chains

P0AEG4  (DSBA_ECOLI) -  Thiol:disulfide interchange protein DsbA from Escherichia coli (strain K12)

Seq: 208 a.a.

Struc: 188 a.a.

DOI no: 10.1021/acs.jmedchem.0c00111

J Med Chem 63:6863-6875 (2020)

PubMed id: 32529824

Rapid Elaboration of Fragments into Leads by X-ray Crystallographic Screening of Parallel Chemical Libraries (REFiL_X).

M.R.Bentley, O.V.Ilyichova, G.Wang, M.L.Williams, G.Sharma, W.S.Alwan, R.L.Whitehouse, B.Mohanty, P.J.Scammells, B.Heras, J.L.Martin, M.Totsika, B.Capuano, B.C.Doak, M.J.Scanlon.

ABSTRACT

A bottleneck in fragment-based lead development is the lack of systematic approaches to elaborate the initial fragment hits, which usually bind with low affinity to their target. Herein, we describe an analysis using X-ray crystallography of a diverse library of compounds prepared using microscale parallel synthesis. This approach yielded an 8-fold increase in affinity and detailed structural information for the resulting complex, providing an efficient and broadly applicable approach to early fragment development.