3HWX

Crystal structure of menaquinone synthesis protein MenD from E. coli in complex with ThDP

Summary for 3HWX

• Entry DOI: 10.2210/pdb3hwx/pdb
• Related: 3FLM
• Descriptor: 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase, SODIUM ION, THIAMINE DIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: menaquinone, thdp, mg, vitamin k2, carboxylase, magnesium, manganese, menaquinone biosynthesis, metal-binding, thiamine pyrophosphate, transferase
• Biological source: Escherichia coli
• Total number of polymer chains: 8
• Total formula weight: 495724.61

Authors

Priyadarshi, A.,Hwang, K.Y. (deposition date: 2009-06-19, release date: 2009-11-03, Last modification date: 2023-11-01)

Primary citation

Priyadarshi, A.,Kim, E.E.,Hwang, K.Y.
Structural and functional analysis of Vitamin K2 synthesis protein MenD.
Biochem.Biophys.Res.Commun., 388:748-751, 2009

PubMed Abstract: Here we describe in detail the crystal structures of the Vitamin K(2) synthesis protein MenD, from Escherichia coli, in complex with thiamine diphosphate (ThDP) and oxoglutarate, and the effects of cofactor and substrate on its structural stability. This is the first reported structure of MenD in complex with oxoglutarate. The residues Gly472 to Phe488 of the active site region are either disordered, or in an open conformation in the MenD oxoglutarate complex structure, but adopt a closed conformation in the MenD ThDP complex structure. Biospecific-interaction analysis using surface plasmon resonance (SPR) technology reveals an affinity for ThDP and oxoglutarate in the nanomolar range. Biochemical and structural analysis confirmed that MenD is highly dependent on ThDP for its structural stability. Our structural results combined with the biochemical assay reveal novel features of the enzyme that could be utilized in a program of rational structure-based drug design, as well as in helping to enhance our knowledge of the menaquinone synthesis pathway in greater detail.

PubMed: 19703421
DOI: 10.1016/j.bbrc.2009.08.093

Experimental method

X-RAY DIFFRACTION (2.6 Å)