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

Autor: Petrenko DE; National Research Center 'Kurchatov Institute', 123182 Moscow, Russia., Karlinsky DM; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia., Gordeeva VD; Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia., Arapidi GP; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia.; Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia.; Moscow Institute of Physics and Technology (National Research University), Phystech School of Biological and Medical Physics, 117303 Moscow, Russia., Britikova EV; Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, 220141 Minsk, Belarus., Britikov VV; Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, 220141 Minsk, Belarus., Nikolaeva AY; National Research Center 'Kurchatov Institute', 123182 Moscow, Russia., Boyko KM; A.N. Bach Institute of Biochemistry, Federal Research Center of Biotechnology of the Russian Academy of Sciences, 119071 Moscow, Russia., Timofeev VI; Shubnikov Institute of Crystallography, Federal Scientific Research Centre 'Crystallography and Photonics' of the Russian Academy of Sciences, 119333 Moscow, Russia., Kuranova IP; Shubnikov Institute of Crystallography, Federal Scientific Research Centre 'Crystallography and Photonics' of the Russian Academy of Sciences, 119333 Moscow, Russia., Mikhailova AG; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia., Bocharov EV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia.; Moscow Institute of Physics and Technology (National Research University), Phystech School of Biological and Medical Physics, 117303 Moscow, Russia., Rakitina TV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Jan 24; Vol. 24 (3). Date of Electronic Publication: 2023 Jan 24.
DOI: 10.3390/ijms24032286
Abstrakt: 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.
Databáze: MEDLINE
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