1T8O

CRYSTAL STRUCTURE OF THE P1 TRP BPTI MUTANT- BOVINE CHYMOTRYPSIN COMPLEX

Summary for 1T8O

• Entry DOI: 10.2210/pdb1t8o/pdb
• Related: 1CBW 1MTN 1P2M 1P2N 1P2O 1P2Q 1T7C 1T8L 1T8M 1T8N
• Descriptor: Chymotrypsin A, Pancreatic trypsin inhibitor, SULFATE ION, ... (4 entities in total)
• Functional Keywords: chymotrypsin, serine proteinase, bovine pancreatic trypsin inhibitor, bpti, protein-protein interaction, non-cognate binding, s1 pocket, primary specificity, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Bos taurus (cattle); More
• Cellular location: Secreted, extracellular space: P00766; Secreted: P00974
• Total number of polymer chains: 4
• Total formula weight: 65465.82

Authors

Czapinska, H.,Helland, R.,Otlewski, J.,Smalas, A.O. (deposition date: 2004-05-13, release date: 2005-03-08, Last modification date: 2024-10-16)

Primary citation

Czapinska, H.,Helland, R.,Smalas, A.O.,Otlewski, J.
Crystal structures of five bovine chymotrypsin complexes with P1 BPTI variants.
J.Mol.Biol., 344:1005-1020, 2004

PubMed Abstract: The bovine chymotrypsin-bovine pancreatic trypsin inhibitor (BPTI) interaction belongs to extensively studied models of protein-protein recognition. The accommodation of the inhibitor P1 residue in the S1 binding site of the enzyme forms the hot spot of this interaction. Mutations introduced at the P1 position of BPTI result in a more than five orders of magnitude difference of the association constant values with the protease. To elucidate the structural aspects of the discrimination between different P1 residues, crystal structures of five bovine chymotrypsin-P1 BPTI variant complexes have been determined at pH 7.8 to a resolution below 2 A. The set includes polar (Thr), ionizable (Glu, His), medium-sized aliphatic (Met) and large aromatic (Trp) P1 residues and complements our earlier studies of the interaction of different P1 side-chains with the S1 pocket of chymotrypsin. The structures have been compared to the complexes of proteases with similar and dissimilar P1 preferences, including Streptomyces griseus proteases B and E, human neutrophil elastase, crab collagenase, bovine trypsin and human thrombin. The S1 sites of these enzymes share a common general shape of significant rigidity. Large and branched P1 residues adapt in their complexes similar conformations regardless of the polarity and size differences between their S1 pockets. Conversely, long and flexible residues such as P1 Met are present in the disordered form and display a conformational diversity despite similar inhibitory properties with respect to most enzymes studied. Thus, the S1 specificity profiles of the serine proteases appear to result from the precise complementarity of the P1-S1 interface and minor conformational adjustments occurring upon the inhibitor binding.

PubMed: 15544809
DOI: 10.1016/j.jmb.2004.09.088

Experimental method

X-RAY DIFFRACTION (1.7 Å)