Crystal structures of thrombin with thiazole-containing inhibitors: probes of the S1' binding site

Structure

x-ray diffraction · 3 distinct chains · 16% helix, 31% strand (DSSP).

Ligands and binding sites

• QWE · amino{[(4S)-4-({[5-(dimethylamino)naphthalen-1-yl]sulfonyl}amino)-5-oxo-5-{(2R)-2-[3-oxo-3-(1,3-thiazol-2-yl)propyl]pip eridin-1-yl}pentyl]amino}methaniminium · ligand · chains H
• NA · Sodium ion · metal · 2 copies · chains H

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

Pockets

1 pocket found on a 1 Å grid, 1 with a druggability of 0.5 or more.

Interfaces

2 interfaces between chains.

• L–H · 1067 Ų buried · 24 hydrogen bonds · protein-protein
• H–I · 535 Ų buried · 6 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 4 disulfide, 1 modified (disulfide, sulfation).

Compared structures

• 1A4W · Crystal structures of thrombin with thiazole-containing inhibitors: probes of the S1'… · the same entry in another collection · chain L against L, TM-score 1.00
• P00734 · AlphaFold monomer V2.0 prediction for prothrombin (P00734) · a predicted model of the same protein · chain H against A, TM-score 0.93
• P09945 · AlphaFold monomer V2.0 prediction for hirudin variant-2 (P09945) · a predicted model of the same protein · chain I against A, TM-score 0.53

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 P00734
• Every structure of UniProt P09945
• Elsewhere: RCSB PDB 1A4W · PDBe 1A4W · UniProt P00734 · UniProt P09945