7P4M

Structure of the quinolinate synthase Y107F variant in an empty open form

7P4M の概要

• エントリーDOI: 10.2210/pdb7p4m/pdb
• 分子名称: Quinolinate synthase A, IRON/SULFUR CLUSTER, FE3-S4 CLUSTER, ... (5 entities in total)
• 機能のキーワード: nad biosynthesis, iron sulfur cluster, active site cavity, transferase
• 由来する生物種: Thermotoga maritima MSB8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35358.94

構造登録者

Volbeda, A. (登録日: 2021-07-12, 公開日: 2021-09-29, 最終更新日: 2024-01-31)

主引用文献

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

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: 34609124
DOI: 10.1021/acschembio.1c00541

実験手法

X-RAY DIFFRACTION (1.55 Å)