4ZK6
Crystallographic Capture of Quinolinate Synthase (NadA) from Pyrococcus horikoshii in its Substrates and Product-Bound States
Summary for 4ZK6
| Entry DOI | 10.2210/pdb4zk6/pdb |
| Related | 4ZKZ 5FEV 5FFK |
| Descriptor | Quinolinate synthase A, IRON/SULFUR CLUSTER, QUINOLINIC ACID, ... (7 entities in total) |
| Functional Keywords | quinolicnic acid, biosynthesis of nicotinamide adenine dinucleotide., transferase |
| Biological source | Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3) |
| Total number of polymer chains | 2 |
| Total formula weight | 69698.53 |
| Authors | Esakova, O.A.,Grove, T.L.,Saunders, A.H.,Yennawar, N.H.,Booker, S.J. (deposition date: 2015-04-29, release date: 2016-06-29, Last modification date: 2023-09-27) |
| Primary citation | Esakova, O.A.,Silakov, A.,Grove, T.L.,Saunders, A.H.,McLaughlin, M.I.,Yennawar, N.H.,Booker, S.J. Structure of Quinolinate Synthase from Pyrococcus horikoshii in the Presence of Its Product, Quinolinic Acid. J.Am.Chem.Soc., 138:7224-7227, 2016 Cited by PubMed Abstract: Quinolinic acid (QA) is a common intermediate in the biosynthesis of nicotinamide adenine dinucleotide (NAD(+)) and its derivatives in all organisms that synthesize the molecule de novo. In most prokaryotes, it is formed from the condensation of dihydroxyacetone phosphate (DHAP) and aspartate-enamine by the action of quinolinate synthase (NadA). NadA contains a [4Fe-4S] cluster cofactor with a unique, non-cysteinyl-ligated, iron ion (Fea), which is proposed to bind the hydroxyl group of a postulated intermediate in the last step of the reaction to facilitate a dehydration. However, direct evidence for this role in catalysis has yet to be provided. Herein, we present the structure of NadA in the presence of the product of its reaction, QA. We find that N1 and the C7 carboxylate group of QA ligate to Fea in a bidentate fashion, which is confirmed by Hyperfine Sublevel Correlation (HYSCORE) spectroscopy. This binding mode would place the C5 hydroxyl group of the postulated final intermediate distal to Fea and virtually incapable of coordinating to it. The structure shows that three strictly conserved amino acids, Glu198, Tyr109, and Tyr23, are in close proximity to the bound product. Substitution of these amino acids with Gln, Phe, and Phe, respectively, leads to complete loss of activity. PubMed: 27224840DOI: 10.1021/jacs.6b02708 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.895 Å) |
Structure validation
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