1K4L

Crystal Structure of 3,4-dihydroxy-2-butanone 4-phosphate synthase in complex with two Manganese ions

Summary for 1K4L

• Entry DOI: 10.2210/pdb1k4l/pdb
• Related: 1K49 1K4I
• Descriptor: 3,4-Dihydroxy-2-Butanone 4-Phosphate Synthase, SULFATE ION, MANGANESE (II) ION, ... (4 entities in total)
• Functional Keywords: dihydroxybutanone phosphate synthase, riboflavin biosynthesis, antimicrobial target, structure-based design, isomerase
• Biological source: Magnaporthe grisea
• Total number of polymer chains: 1
• Total formula weight: 25338.34

Authors

Liao, D.-I.,Zheng, Y.-J.,Viitanen, P.V.,Jordan, D.B. (deposition date: 2001-10-08, release date: 2002-03-06, Last modification date: 2023-08-16)

Primary citation

Liao, D.I.,Zheng, Y.J.,Viitanen, P.V.,Jordan, D.B.
Structural definition of the active site and catalytic mechanism of 3,4-dihydroxy-2-butanone-4-phosphate synthase.
Biochemistry, 41:1795-1806, 2002

PubMed Abstract: X-ray crystal structures of L-3,4-dihydroxy-2-butanone-4-phosphate synthase from Magnaporthe grisea are reported for the E-SO(4)(2-), E-SO(4)(2-)-Mg(2+), E-SO(4)(2)(-)-Mn(2+), E-SO(4)(2)(-)-Mn(2+)-glycerol, and E-SO(4)(2)(-)-Zn(2+) complexes with resolutions that extend to 1.55, 0.98, 1.60, 1.16, and 1.00 A, respectively. Active-site residues of the homodimer are fully defined. The structures were used to model the substrate ribulose 5-phosphate in the active site with the phosphate group anchored at the sulfate site and the placement of the ribulose group guided by the glycerol site. The model includes two Mg(2+) cations that bind to the oxygen substituents of the C2, C3, C4, and phosphate groups of the substrate, the side chains of Glu37 and His153, and water molecules. The position of the metal cofactors and the substrate's phosphate group are further stabilized by an extensive hydrogen-bond and salt-bridge network. On the basis of their proximity to the substrate's reaction participants, the imidazole of an Asp99-His136 dyad from one subunit, the side chains of the Asp41, Cys66, and Glu174 residues from the other subunit, and Mg(2+)-activated water molecules are proposed to serve specific roles in the catalytic cycle as general acid-base functionalities. The model suggests that during the 1,2-shift step of the reaction, the substrate's C3 and C4 hydroxyl groups are cis to each other. A cis transition state is calculated to have an activation barrier that is 2 kcal/mol greater than that of the trans transition state in the absence of the enzyme.

PubMed: 11827524
DOI: 10.1021/bi015652u

Experimental method

X-RAY DIFFRACTION (1.6 Å)