Thrombin A-Chain: Activation Remnant or Allosteric Effector?

Figure 2

Pymol-generated structure of thrombin using the PDB 3GIS coordinates of Ser195Ala thrombin [8]. (a) Interactions between the A-chain and the B-chain of thrombin (B-chain residues are labeled in blue, the 36-amino acid residue A-chain is colored in green, and the covalently bound A13 peptide segment is colored magenta. The covalent disulfide bridge between the A- and B-chains is through Cys1(93)-Cys122, as shown in orange. Hydrogen bonds are colored yellow and residue numbering is based on chymotrypsinogen, with prothrombin numbering for the A-chain provided in brackets. The A-chain is stabilized by the Asp1a(92)-Lys9(301) and Arg14d(310)-Glu13(314) ion pairs and the ion quartet Arg4(96)-Glu8(300)-Asp14(306)-Glu14c(309). The ionic interactions include Glu8(300)-Lys202-Glu14c(309), Asp14(306)-Arg137, Lys14a(307)-Glu23, and Glu14e(311)-Lys135-Asn159-Tyr194a. Hydrophobic stacking interactions include Tyr14j(316)-Pro204 and Phe1m(280)-Phe1l(281)-Phe1g(286) in the A13 peptide of the A-chain. (b) Thrombin structure showing active site residues in red and location of the A-chain on the opposite face of the molecule.