3GIC

Structure of thrombin mutant delta(146-149e) in the free form

Summary for 3GIC

• Entry DOI: 10.2210/pdb3gic/pdb
• Descriptor: Thrombin light chain, Thrombin heavy chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: serine protease, chymotrypsin fold, acute phase, blood coagulation, cleavage on pair of basic residues, disease mutation, disulfide bond, gamma-carboxyglutamic acid, glycoprotein, hydrolase, kringle, protease, secreted, zymogen
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 33109.89

Authors

Bah, A.,Carrell, C.J.,Chen, Z.,Gandhi, P.S.,Di Cera, E. (deposition date: 2009-03-05, release date: 2009-06-02, Last modification date: 2023-09-06)

Primary citation

Bah, A.,Carrell, C.J.,Chen, Z.,Gandhi, P.S.,Di Cera, E.
Stabilization of the E* form turns thrombin into an anticoagulant.
J.Biol.Chem., 284:20034-20040, 2009

PubMed Abstract: Previous studies have shown that deletion of nine residues in the autolysis loop of thrombin produces a mutant with an anticoagulant propensity of potential clinical relevance, but the molecular origin of the effect has remained unresolved. The x-ray crystal structure of this mutant solved in the free form at 1.55 A resolution reveals an inactive conformation that is practically identical (root mean square deviation of 0.154 A) to the recently identified E* form. The side chain of Trp(215) collapses into the active site by shifting > 10 A from its position in the active E form, and the oxyanion hole is disrupted by a flip of the Glu(192)-Gly(193) peptide bond. This finding confirms the existence of the inactive form E* in essentially the same incarnation as first identified in the structure of the thrombin mutant D102N. In addition, it demonstrates that the anticoagulant profile often caused by a mutation of the thrombin scaffold finds its likely molecular origin in the stabilization of the inactive E* form that is selectively shifted to the active E form upon thrombomodulin and protein C binding.

PubMed: 19473969
DOI: 10.1074/jbc.M109.012344

Experimental method

X-RAY DIFFRACTION (1.55 Å)