Steve Ealick's Research Group
Mesorhizobium loti HMPD Decarboxylase
Mesorhizobium loti 3-hydroxy-2-methylpyridine-4,5-dicarboxylate decarboxylase (HMPDdc) is involved in the catabolism pathway of pyridoxal 5′-phosphate (PLP) . Specifically, it facilitates the decarboxylation of 3-hydroxy-2-methylpyridine-4,5-dicarboxylate (HMPD) to 3-hydroxy-2-methylpyridine-5-carboxylate. The structure was solved by SAD phasing. As a result, it is hypothesized that catalysis of such decarboxylations proceeds by an aldolase-like mechanism.
The monomer is composed of a single domain with an αβα fold. The β-sheet forms a half-barrel with four a-helices flanking one side of the β-sheet and two α-helices flanking the opposite side.
|The quaternary structure of HMPDdc is a tetramer formed by using the fourfold crystallographic axis of the space group I4 A channel with a diameter of 10 Å runs through the tetramer. The opening of the channel much wider at the top (near the N and C termini) and nearly closed on the bottom|
The presumed active site forms near the hydrophobic patch at the interface between two subunits. The cleft is found in the middle of the tetramer and lies closer to the external solvent than to the channel that runs through the tetramer. A large unexpected peak in the electron density was found in this cleft and was modeled as a manganese ion. Adjacent to the bound metal is a pocket that could potentially accommodate HMPD.
Mukherjee T, McCulloch KM, Ealick SE and Begley TP. Gene identification and structural characterization of the PLP degradative protein 3-hydroxy-2-methylpyridine-4,5-dicarboxylate decarboxylase from Mesorhizobium loti MAFF303099. Biochemistry 46:13606-13615 (2007). PubMed.