1AMH

UNCOMPLEXED RAT TRYPSIN MUTANT WITH ASP 189 REPLACED WITH SER (D189S)

Summary for 1AMH

• Entry DOI: 10.2210/pdb1amh/pdb
• Descriptor: ANIONIC TRYPSIN, CALCIUM ION (3 entities in total)
• Functional Keywords: serine protease, activation domain, substrate specificity hydrolase, hydrolase
• Biological source: Rattus rattus (black rat)
• Cellular location: Secreted, extracellular space: P00763
• Total number of polymer chains: 2
• Total formula weight: 47653.81

Authors

Szabo, E.,Bocskei, Z.S.,Naray-Szabo, G.,Graf, L. (deposition date: 1997-06-17, release date: 1997-12-24, Last modification date: 2024-10-23)

Primary citation

Szabo, E.,Bocskei, Z.,Naray-Szabo, G.,Graf, L.
The three-dimensional structure of Asp189Ser trypsin provides evidence for an inherent structural plasticity of the protease.
Eur.J.Biochem., 263:20-26, 1999

PubMed Abstract: Trypsin mutant Asp189Ser, first described by Gráf et al. [Gráf, L., Jancsó, A., Szilágyi, L., Hegyi, G., Pintér, K., Náray-Szabó, G., Hepp, J., Medzihradszky, K. & Rutter, W.J. (1988) Proc. Natl Acad. Sci. USA 85, 4961-4965] has played an important role in recent studies on the structural basis of substrate-specific catalysis by serine proteases. The present work reports the three-dimensional structure of this mutant crystallized in unliganded form: the first unliganded rat trypsin structure reported. The X-ray structure of the Asp189Ser trypsin mutant in complex with bovine pancreatic trypsin inhibitor is already known. The X-ray structure of free Asp189Ser rat trypsin revealed that the single amino acid mutation at the bottom of the substrate binding pocket of trypsin resulted in extensive structural changes around the mutated site and in dimerization of the mutant, in contrast with the complexed enzyme the structure of which is practically the same as that of wild-type trypsin. The structural rearrangement in the mutant was shown to be restricted to the activation domain region providing further evidence for the allosteric property of this structural-functional unit of the enzyme. This study supports our view that the plasticity of the activation domain may play an important role in the mechanism of substrate-specific serine protease action.

PubMed: 10429182
DOI: 10.1046/j.1432-1327.1999.00452.x

Experimental method

X-RAY DIFFRACTION (2.5 Å)