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Crystal Structure of Inhibitor-Bound Bacterial Oligopeptidase B in the Closed State: Similarity and Difference between Protozoan and Bacterial Enzymes.

Dmitry E PetrenkoDavid M KarlinskyVeronika D GordeevaGeorgij P ArapidiElena V BritikovaVladimir V BritikovAlena Y NikolaevaKonstantin M BoykoVladimir I TimofeevInna P KuranovaAnna G MikhailovaEduard V BocharovTatiana V Rakitina
Published in: International journal of molecular sciences (2023)
The crystal structure of bacterial oligopeptidase B from Serratia proteamaculans (SpOpB) in complex with a chloromethyl ketone inhibitor was determined at 2.2 Å resolution. SpOpB was crystallized in a closed (catalytically active) conformation. A single inhibitor molecule bound simultaneously to the catalytic residues S532 and H652 mimicked a tetrahedral intermediate of the catalytic reaction. A comparative analysis of the obtained structure and the structure of OpB from Trypanosoma brucei (TbOpB) in a closed conformation showed that in both enzymes, the stabilization of the D-loop (carrying the catalytic D) in a position favorable for the formation of a tetrahedral complex occurs due to interaction with the neighboring loop from the β-propeller. However, the modes of interdomain interactions were significantly different for bacterial and protozoan OpBs. Instead of a salt bridge (as in TbOpB), in SpOpB, a pair of polar residues following the catalytic D617 and a pair of neighboring arginine residues from the β-propeller domain formed complementary oppositely charged surfaces. Bioinformatics analysis and structural modeling show that all bacterial OpBs can be divided into two large groups according to these two modes of D-loop stabilization in closed conformations.
Keyphrases
  • crystal structure
  • transcription factor
  • bioinformatics analysis
  • molecular dynamics simulations
  • staphylococcus aureus
  • single molecule
  • cystic fibrosis