6F4L

Structure of quinolinate synthase with inhibitor-derived quinolinate

Summary for 6F4L

• Entry DOI: 10.2210/pdb6f4l/pdb
• Descriptor: Quinolinate synthase A, IRON/SULFUR CLUSTER, QUINOLINIC ACID, ... (6 entities in total)
• Functional Keywords: nad biosynthesis, iron sulfur cluster, transferase
• Biological source: Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
• Cellular location: Cytoplasm : Q9X1X7
• Total number of polymer chains: 1
• Total formula weight: 35418.10

Authors

Volbeda, A.,Fontecilla-Camps, J.C. (deposition date: 2017-11-29, release date: 2018-04-25, Last modification date: 2024-01-17)

Primary citation

Volbeda, A.,Saez Cabodevilla, J.,Darnault, C.,Gigarel, O.,Han, T.H.,Renoux, O.,Hamelin, O.,Ollagnier-de-Choudens, S.,Amara, P.,Fontecilla-Camps, J.C.
Crystallographic Trapping of Reaction Intermediates in Quinolinic Acid Synthesis by NadA.
ACS Chem. Biol., 13:1209-1217, 2018

PubMed Abstract: NadA is a multifunctional enzyme that condenses dihydroxyacetone phosphate (DHAP) with iminoaspartate (IA) to generate quinolinic acid (QA), the universal precursor of the nicotinamide adenine dinucleotide (NAD(P)) cofactor. Using X-ray crystallography, we have (i) characterized two of the reaction intermediates of QA synthesis using a "pH-shift" approach and a slowly reacting Thermotoga maritima NadA variant and (ii) observed the QA product, resulting from the degradation of an intermediate analogue, bound close to the entrance of a long tunnel leading to the solvent medium. We have also used molecular docking to propose a condensation mechanism between DHAP and IA based on two previously published Pyrococcus horikoshi NadA structures. The combination of reported data and our new results provide a structure-based complete catalytic sequence of QA synthesis by NadA.

PubMed: 29641168
DOI: 10.1021/acschembio.7b01104

Experimental method

X-RAY DIFFRACTION (2.3 Å)