2A88

Crystal structure of A Pantothenate synthetase, apo enzyme in C2 space group

Summary for 2A88

• Entry DOI: 10.2210/pdb2a88/pdb
• Related: 1MOP 1N2B 1N2H 2A7X 2A84 2A86
• Descriptor: Pantoate--beta-alanine ligase, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: dimer, rossmann fold, structural genomics, psi, protein structure initiative, tb structural genomics consortium, tbsgc, ligase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 1
• Total formula weight: 31780.35

Authors

Wang, S.,Eisenberg, D.,TB Structural Genomics Consortium (TBSGC) (deposition date: 2005-07-07, release date: 2006-02-21, Last modification date: 2023-08-23)

Primary citation

Wang, S.,Eisenberg, D.
Crystal Structure of the Pantothenate Synthetase from Mycobacterium tuberculosis, Snapshots of the Enzyme in Action.
Biochemistry, 45:1554-1561, 2006

PubMed Abstract: Pantothenate synthetase (PS) from Mycobacterium tuberculosis represents a potential target for antituberculosis drugs. PS catalyzes the ATP-dependent condensation of pantoate and beta-alanine to form pantothenate. Previously, we determined the crystal structure of PS from M. tuberculosis and its complexes with AMPCPP, pantoate, and pantoyl adenylate. Here, we describe the crystal structure of this enzyme complexed with AMP and its last substrate, beta-alanine, and show that the phosphate group of AMP serves as an anchor for the binding of beta-alanine. This structure confirms that binding of beta-alanine in the active site cavity can occur only after formation of the pantoyl adenylate intermediate. A new crystal form was also obtained; it displays the flexible wall of the active site cavity in a conformation incapable of binding pantoate. Soaking of this crystal form with ATP and pantoate gives a fully occupied complex of PS with ATP. Crystal structures of these complexes with substrates, the reaction intermediate, and the reaction product AMP provide a step-by-step view of the PS-catalyzed reaction. A detailed reaction mechanism and its implications for inhibitor design are discussed.

PubMed: 16460002
DOI: 10.1021/bi051873e

Experimental method

X-RAY DIFFRACTION (1.7 Å)