1TWX

Crystal structure of the thrombin mutant D221A/D222K

Summary for 1TWX

• Entry DOI: 10.2210/pdb1twx/pdb
• Descriptor: Prothrombin, Hirudin, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: thrombin, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 34566.56

Authors

Pineda, A.O.,Zhang, E.,Guinto, E.R.,Savvides, S.N.,Tulinsky, A.,Di Cera, E. (deposition date: 2004-07-01, release date: 2005-04-19, Last modification date: 2023-11-15)

Primary citation

Pineda, A.O.,Zhang, E.,Guinto, E.R.,Savvides, S.N.,Tulinsky, A.,Di Cera, E.
Crystal structure of the thrombin mutant D221A/D222K: the Asp222:Arg187 ion-pair stabilizes the fast form
Biophys.Chem., 112:253-256, 2004

PubMed Abstract: The thrombin mutant D221A/D222K (ARK) does not bind Na+ and has interesting functional properties intermediate between those of the slow and fast forms of wild type. We solved the X-ray crystal structure of ARK bound at exosite I with a fragment of hirudin at 2.4-A resolution. The structure shows a slight collapse of the 186 and 220 loops into the Na+ binding site due to disruption of the Asp222:Arg187 ion-pair. The backbone O atoms of Arg221a and Lys224 are shifted into conformations that eliminate optimal interaction with Na+. A paucity of solvent molecules in the Na+ binding site is also noted, by analogy to what is seen in the structure of the slow form. These findings reinforce the crucial role of the Asp222:Arg187 ion-pair in stabilizing the fast form of thrombin.

PubMed: 15572256
DOI: 10.1016/j.bpc.2004.07.027

Experimental method

X-RAY DIFFRACTION (2.4 Å)