PDBsum entry 6f2c

Lyase

PDB id: 6f2c

Contents

Protein chains

(+ 6 more) 124 a.a.

Ligands

GOL ×9

Metals

_CL ×19

Waters ×529

PDB id:

6f2c

Name:

Lyase

Title:

Methylglyoxal synthase mgsa from bacillus subtilis

Structure:

Methylglyoxal synthase. Chain: a, d, b, f, c, e, h, k, g, i, l, j. Fragment: residues 3- 610. Synonym: mgs. Engineered: yes

Source:

Bacillus subtilis (strain 168). Organism_taxid: 224308. Gene: mgsa, ypjf, bsu22480. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.34Å R-factor: 0.173 R-free: 0.207

Authors:

A.Dickmanns,P.Neumann,R.Ficner

Key ref:

A.Dickmanns et al. (2018). Structural basis for the regulatory interaction of the methylglyoxal synthase MgsA with the carbon flux regulator Crh in J Biol Chem, 293, 5781-5792. PubMed id: 29514981

Date:

24-Nov-17 Release date: 07-Mar-18

Protein chains

P42980  (MGSA_BACSU) -  Methylglyoxal synthase from Bacillus subtilis (strain 168)

Seq: 137 a.a.

Struc: 124 a.a.

Enzyme reactions

• Enzyme class: E.C.4.2.3.3 - methylglyoxal synthase.
• Reaction: dihydroxyacetone phosphate = methylglyoxal + phosphate

dihydroxyacetone phosphate = methylglyoxal (Bound ligand (Het Group name = GOL) matches with 83.33% similarity) + phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

J Biol Chem 293:5781-5792 (2018)

PubMed id: 29514981

Structural basis for the regulatory interaction of the methylglyoxal synthase MgsA with the carbon flux regulator Crh in

A.Dickmanns, C.P.Zschiedrich, J.Arens, I.Parfentev, J.Gundlach, R.Hofele, P.Neumann, H.Urlaub, B.Görke, R.Ficner, J.Stülke.

ABSTRACT

Utilization of energy-rich carbon sources such as glucose is fundamental to the evolutionary success of bacteria. Glucose can be catabolized via glycolysis for feeding the intermediary metabolism. The methylglyoxal synthase MgsA produces methylglyoxal from the glycolytic intermediate dihydroxyacetone phosphate. Methylglyoxal is toxic, requiring stringent regulation of MgsA activity. In the Gram-positive bacterium Bacillus subtilis, an interaction with the phosphoprotein Crh controls MgsA activity. In the absence of preferred carbon sources, Crh is present in the nonphosphorylated state and binds to and thereby inhibits MgsA. To better understand the mechanism of regulation of MgsA, here we performed biochemical and structural analyses of B. subtilis MgsA and of its interaction with Crh. Our results indicated that MgsA forms a hexamer (i.e. a trimer of dimers) in the crystal structure, whereas it seems to exist in an equilibrium between a dimer and hexamer in solution. In the hexamer, two alternative dimers could be distinguished, but only one appeared to prevail in solution. Further analysis strongly suggested that the hexamer is the biologically active form. In vitro cross-linking studies revealed that Crh interacts with the N-terminal helices of MgsA and that the Crh-MgsA binding inactivates MgsA by distorting and thereby blocking its active site. In summary, our results indicate that dimeric and hexameric MgsA species exist in an equilibrium in solution, that the hexameric species is the active form, and that binding to Crh deforms and blocks the active site in MgsA.