5BUQ

Unliganded Form of O-succinylbenzoate Coenzyme A Synthetase (MenE) from Bacillus Subtilis, Solved at 1.98 Angstroms

Summary for 5BUQ

• Entry DOI: 10.2210/pdb5buq/pdb
• Related: 5BUR 5BUS
• Descriptor: 2-succinylbenzoate--CoA ligase, ACETATE ION, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: apo, atp, amp, enzyme mechanism, protein conformation, vitamin k2, adenylate forming enzyme, domain alteration, open-closed conformational change, ligase
• Biological source: Bacillus subtilis (strain 168)
• Total number of polymer chains: 2
• Total formula weight: 110637.36

Authors

Chen, Y.,Sun, Y.,Song, H.,Guo, Z. (deposition date: 2015-06-04, release date: 2015-08-26, Last modification date: 2023-11-08)

Primary citation

Chen, Y.,Sun, Y.,Song, H.,Guo, Z.
Structural Basis for the ATP-dependent Configuration of Adenylation Active Site in Bacillus subtilis o-Succinylbenzoyl-CoA Synthetase
J.Biol.Chem., 290:23971-23983, 2015

PubMed Abstract: o-Succinylbenzoyl-CoA synthetase, or MenE, is an essential adenylate-forming enzyme targeted for development of novel antibiotics in the menaquinone biosynthesis. Using its crystal structures in a ligand-free form or in complex with nucleotides, a conserved pattern is identified in the interaction between ATP and adenylating enzymes, including acyl/aryl-CoA synthetases, adenylation domains of nonribosomal peptide synthetases, and luciferases. It involves tight gripping interactions of the phosphate-binding loop (P-loop) with the ATP triphosphate moiety and an open-closed conformational change to form a compact adenylation active site. In MenE catalysis, this ATP-enzyme interaction creates a new binding site for the carboxylate substrate, allowing revelation of the determinants of substrate specificities and in-line alignment of the two substrates for backside nucleophilic substitution reaction by molecular modeling. In addition, the ATP-enzyme interaction is suggested to play a crucial catalytic role by mutation of the P-loop residues hydrogen-bonded to ATP. Moreover, the ATP-enzyme interaction has also clarified the positioning and catalytic role of a conserved lysine residue in stabilization of the transition state. These findings provide new insights into the adenylation half-reaction in the domain alteration catalytic mechanism of the adenylate-forming enzymes.

PubMed: 26276389
DOI: 10.1074/jbc.M115.676304

Experimental method

X-RAY DIFFRACTION (1.98 Å)