8VAG

Crystal structure of MnII/MnII CtCADD from Chlamydia trachomatis

8VAG の概要

• エントリーDOI: 10.2210/pdb8vag/pdb
• 分子名称: 4-aminobenzoate synthase, MANGANESE (II) ION (3 entities in total)
• 機能のキーワード: mnii reconstituted form, oxidoreductase
• 由来する生物種: Chlamydia trachomatis D/UW-3/CX
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55758.32

構造登録者

Phan, H.N.,Swartz, P.D.,Makris, T.M. (登録日: 2023-12-11, 公開日: 2024-11-06, 最終更新日: 2024-11-27)

主引用文献

Phan, H.N.,Swartz, P.D.,Gangopadhyay, M.,Guo, Y.,Smirnov, A.I.,Makris, T.M.
Assembly of a Heterobimetallic Fe/Mn Cofactor in the para -Aminobenzoate Synthase Chlamydia Protein Associating with Death Domains (CADD) Initiates Long-Range Radical Hole-Hopping.
Biochemistry, 63:3020-3029, 2024

PubMed Abstract: Chlamydia protein associating with death domains (CADD) is involved in the biosynthesis of -aminobenzoic acid (pABA) for integration into folate, a critical cofactor that is required for pathogenic survival. CADD activates dioxygen and utilizes its own tyrosine and lysine as synthons to furnish the carboxylate, carbon backbone, and amine group of pABA in a complex multistep mechanism. Unlike other members of the heme oxygenase-like dimetal oxidase (HDO) superfamily that typically house an Fe cofactor, previous activity studies have shown that CADD likely uses a heterobimetallic Fe/Mn center. The structure of the Fe/Mn cofactor and how the conserved HDO scaffold mediates metal selectivity have remained enigmatic. Adopting an metalation approach, CADD was solved in the apo, Fe, Mn, and catalytically active Fe/Mn forms to identify the probable site for Mn binding. The analysis of CADD active-site variants further reinforces the importance of the secondary coordination sphere on cofactor preference for competent pABA formation. Rapid kinetic optical and electron paramagnetic resonance (EPR) studies show that the heterobimetallic cofactor selectively reacts with dioxygen and likely initiates pABA assembly through the formation of a transient tyrosine radical intermediate and a resultant heterobimetallic Mn/Fe cluster.

PubMed: 39471288
DOI: 10.1021/acs.biochem.4c00326

実験手法

X-RAY DIFFRACTION (2.61 Å)