7QIT

CRYSTAL STRUCTURE OF THE P1 trifluoroethylglycine (TfeGly) BPTI MUTANT- BOVINE CHYMOTRYPSIN COMPLEX

Summary for 7QIT

• Entry DOI: 10.2210/pdb7qit/pdb
• Related: 7QIQ 7QIR 7QIS
• Descriptor: Chymotrypsin A chain A, Chymotrypsin A chain B, Chymotrypsin A chain C, ... (7 entities in total)
• Functional Keywords: chymotrypsin, serine proteinase, bovine pancreatic trypsin inhibitor, bpti, protein-protein interaction, s1 pocket, primary specificity, hydrolase-hydrolase inhibitor complex, hydrolase
• Biological source: Bos taurus (cattle); More
• Total number of polymer chains: 8
• Total formula weight: 68284.13

Authors

Dimos, N.,Leppkes, J.,Koksch, B.,Wahl, M.C.,Loll, B. (deposition date: 2021-12-15, release date: 2022-03-09, Last modification date: 2024-11-13)

Primary citation

Leppkes, J.,Dimos, N.,Loll, B.,Hohmann, T.,Dyrks, M.,Wieseke, A.,Keller, B.G.,Koksch, B.
Fluorine-induced polarity increases inhibitory activity of BPTI towards chymotrypsin.
Rsc Chem Biol, 3:773-782, 2022

PubMed Abstract: Substituting the P position in bovine pancreatic trypsin inhibitor (BPTI) is known to heavily influence its inhibitory activity towards serine proteases. Side-chain fluorinated aliphatic amino acids have been shown to alter numerous properties of peptides and proteins and thus are of interest in the context of BPTI. In our study, we systematically investigated the site-specific incorporation of non-canonical amino acids into BPTI by microwave-assisted solid-phase peptide synthesis (SPPS). Inhibitor activity of the variants was tested towards the serine protease α-chymotrypsin. We observed enhanced inhibition of two fluorinated BPTIs compared to wild type and hydrocarbon variants. To further investigate the complexes, we performed X-ray structure analysis. Our findings underline the power fluorine offers as a tool in protein engineering to beneficially alter the effects on phenomena as protein-protein interactions.

PubMed: 35755190
DOI: 10.1039/d2cb00018k

Experimental method

X-RAY DIFFRACTION (1.99 Å)