Molecular modeling studies of L-arabinitol 4-dehydrogenase of Hypocrea jecorina: Its binding interactions with substrate and cofactor

Manish Kumar Tiwari, Jung-Kul Lee

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

L-Arabinitol 4-dehydrogenase (LAD1; EC 1.1.1.12) is an enzyme in the L-arabinose catabolic pathway of fungi that catalyzes the conversion of L-arabinitol into L-xylulose. The primary objective of this work is to identify the catalytic and coenzyme binding domains of LAD1 from Hypocrea jecorina in order to provide better insight into the possible catalytic events in these domains. The 3D structure of NAD+-dependent
LAD1 was developed based on the crystal structure of human sorbitol dehydrogenase as a template. A series ofmolecular mechanics and dynamics operations were performed to find the most stable binding interaction for the enzyme and its ligands. Using the verified model, a docking studywas performed with the substrate L-arabinitol, Zn2+ and NAD+. This study found a catalytic Zn2+ binding domain (Cys66,
His91, Glu92 and Glu176) and a cofactor NAD+ binding domain (Gly202, ILeu204, Gly205, Cys273, Arg229 and Val298) with strong hydrogen bonding contacts with the substrate and cofactor. The binding pockets of the enzyme for L-arabinitol, NAD+, and Zn2+ have been explicitly defined. The results from this study should guide future mutagenesis studies and provide useful clues for engineering enzymes to
improve the utilization of polyols for rare sugar production
Original languageEnglish
JournalJournal of Molecular Graphics and Modelling
Volume28
Pages (from-to)707–713
ISSN1093-3263
DOIs
Publication statusPublished - 2010
Externally publishedYes

Keywords

  • L-Arabinitol 4-dehydrogenase
  • Catalytic Zn2+
  • Cofactor binding domain
  • Hypocrea jecorina
  • Molecular modeling

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