Crystal structure of ILvC, a ketol-acid reductoisomerase, from Streptococcus pneumoniae

Gyuhee Kim, Donghyuk Shin, Sumin Lee, Jaesook Yun, Sangho Lee

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Biosynthesis of branched-chain amino acids (BCAAs), including isoleucine, leucine and valine, is required for survival and virulence of a bacterial pathogen such as Streptococcus pneumoniae. IlvC, a ketol-acid reductoisomerase (E.C. 1.1.1.86) with NADP(H) and Mg2+ as cofactors from the pathogenic Streptococcus pneumoniae (SpIlvC), catalyzes the second step in the BCAA biosynthetic pathway. To elucidate the structural basis for the IlvC-mediated reaction, we determined the crystal structure of SpIlvC at 1.69 Å resolution. The crystal structure of SpIlvC contains an asymmetric dimer in which one subunit is in apo-form and the other in NADP(H) and Mg2+-bound form. Crystallographic analysis combined with an activity assay and small-angle X-ray scattering suggested that SpIlvC retains dimeric arrangement in solution and that D83 in the NADP(H) binding site and E195 in the Mg2+ binding site are the most critical in the catalytic activity of SpIlvC. Crystal structures of SpIlvC mutants (R49E, D83G, D191G and E195S) revealed local conformational changes only in the NADP(H) binding site. Taken together, our results establish the molecular mechanism for understanding functions of SpIlvC in pneumococcal growth and virulence.

Original languageEnglish
Article number551
JournalCrystals
Volume9
Issue number11
DOIs
Publication statusPublished - 2019 Nov

Bibliographical note

Funding Information:
This research was supported by the Next-Generation BioGreen 21 program (PJ01367602) through the Rural Development Administration and the Basic Science Research Program (NRF-2018R1A2B6004367 and NRF-2019R1A6A7076041) and the Science Research Center Program (SRC-2017R1A5A1014560) through the National Research Foundation of Korea (NRF) grants.

Funding Information:
Funding: This research was supported by the Next-Generation BioGreen 21 program (PJ01367602) through the Rural Development Administration and the Basic Science Research Program (NRF-2018R1A2B6004367 and NRF-2019R1A6A7076041) and the Science Research Center Program (SRC-2017R1A5A1014560) through the National Research Foundation of Korea (NRF) grants.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Chemical Engineering(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Inorganic Chemistry

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