Pyrrolopyrimidine inhibitors of DNA gyrase B and topoisomerase IV, part I: structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity.

Structure

x-ray diffraction · 1 distinct chain · 31% helix, 28% strand (DSSP).

Ligands and binding sites

• 1A1 · N-[7-(1H-imidazol-1-yl)-2-(pyridin-3-yl)[1,3]thiazolo[5,4-d]pyrimidin-5-yl]cyclopropanecarboxamide · ligand · 4 copies · chains A, B, C, D
• MG · Magnesium ion · metal · 4 copies · chains A, B, C, D

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

9 pockets found on a 1 Å grid, 5 with a druggability of 0.5 or more.

Interfaces

4 interfaces between chains.

• A–B · 1045 Ų buried · 6 hydrogen bonds · protein-protein
• C–D · 1040 Ų buried · 6 hydrogen bonds · protein-protein
• B–C · 278 Ų buried · 4 hydrogen bonds · protein-protein
• A–D · 93 Ų buried · 0 hydrogen bonds · protein-protein

Compared structures

• 4HYP · Pyrrolopyrimidine inhibitors of dna gyrase b and topoisomerase iv, part i: structure… · the same entry in another collection · chain A against A, TM-score 1.00
• P0AES6 · AlphaFold monomer V2.0 prediction for DNA gyrase subunit B (P0AES6) · a predicted model of the same protein · chain A against A, TM-score 0.96

Analyse

• Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
• Every structure of UniProt P0AES6
• Elsewhere: RCSB PDB 4HYP · PDBe 4HYP · UniProt P0AES6