5VLB

Crystal Structure of Medicago truncatula L-Histidinol Dehydrogenase in Complex with Imidazole

Summary for 5VLB

• Entry DOI: 10.2210/pdb5vlb/pdb
• Related: 5VLC 5VLD
• Descriptor: Histidinol dehydrogenase, chloroplastic, ZINC ION, IMIDAZOLE, ... (5 entities in total)
• Functional Keywords: histidine biosynthesis, zn2+ binding protein, nad binding protein, plant protein, oxidoreductase
• Biological source: Medicago truncatula (Barrel medic)
• Cellular location: Plastid, chloroplast : G7IKX3
• Total number of polymer chains: 6
• Total formula weight: 290606.06

Authors

Ruszkowski, M.,Dauter, Z. (deposition date: 2017-04-25, release date: 2017-09-20, Last modification date: 2023-10-04)

Primary citation

Ruszkowski, M.,Dauter, Z.
Structures of Medicago truncatula L-Histidinol Dehydrogenase Show Rearrangements Required for NAD(+) Binding and the Cofactor Positioned to Accept a Hydride.
Sci Rep, 7:10476-10476, 2017

PubMed Abstract: Plants, lower eukaryotes, bacteria, and archaebacteria synthesise L-histidine (His) in a similar, multistep pathway that is absent in mammals. This makes the His biosynthetic route a promising target for herbicides, antifungal agents, and antibiotics. The last enzyme of the pathway, bifunctional L-histidinol dehydrogenase (HDH, EC 1.1.1.23), catalyses two oxidation reactions: from L-histidinol (HOL) to L-histidinaldehyde and from L-histidinaldehyde to His. Over the course of the reaction, HDH utilises two molecules of NAD as the hydride acceptor. The object of this study was the HDH enzyme from the model legume plant, Medicago truncatula (MtHDH). Three crystal structures complexed with imidazole, HOL, and His with NAD provided in-depth insights into the enzyme architecture, its active site, and the cofactor binding mode. The overall structure of MtHDH is similar to the two bacterial orthologues whose three-dimensional structures have been determined. The three snapshots, with the MtHDH enzyme captured in different states, visualise structural rearrangements that allow for NAD binding for the first time. Furthermore, the MtHDH complex with His and NAD displays the cofactor molecule situated in a way that would allow for a hydride transfer.

PubMed: 28874718
DOI: 10.1038/s41598-017-10859-0

Experimental method

X-RAY DIFFRACTION (2.25 Å)