7P4Q
Structure of the quinolinate synthase S124A variant complexed with citrate
Summary for 7P4Q
| Entry DOI | 10.2210/pdb7p4q/pdb |
| Descriptor | Quinolinate synthase A, IRON/SULFUR CLUSTER, CITRATE ANION, ... (7 entities in total) |
| Functional Keywords | nad biosynthesis, iron sulfur cluster, active site cavity, transferase |
| Biological source | Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) |
| Total number of polymer chains | 1 |
| Total formula weight | 36100.60 |
| Authors | Volbeda, A. (deposition date: 2021-07-12, release date: 2021-09-29, Last modification date: 2024-01-31) |
| Primary citation | Basbous, H.,Volbeda, A.,Amara, P.,Rohac, R.,Martin, L.,Ollagnier de Choudens, S.,Fontecilla-Camps, J.C. Transient Formation of a Second Active Site Cavity during Quinolinic Acid Synthesis by NadA. Acs Chem.Biol., 16:2423-2433, 2021 Cited by PubMed Abstract: Quinolinate synthase, also called NadA, is a [4Fe-4S]-containing enzyme that uses what is probably the oldest pathway to generate quinolinic acid (QA), the universal precursor of the biologically essential cofactor nicotinamide adenine dinucleotide (NAD). Its synthesis comprises the condensation of dihydroxyacetone phosphate (DHAP) and iminoaspartate (IA), which involves dephosphorylation, isomerization, cyclization, and two dehydration steps. The convergence of the three homologous domains of NadA defines a narrow active site that contains a catalytically essential [4Fe-4S] cluster. A tunnel, which can be opened or closed depending on the nature (or absence) of the bound ligand, connects this cofactor to the protein surface. One outstanding riddle has been the observation that the so far characterized active site is too small to bind IA and DHAP simultaneously. Here, we have used site-directed mutagenesis, X-ray crystallography, functional analyses, and molecular dynamics simulations to propose a condensation mechanism that involves the transient formation of a second active site cavity to which one of the substrates can migrate before this reaction takes place. PubMed: 34609124DOI: 10.1021/acschembio.1c00541 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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