Excision of a Protein-Derived Amine for p-Aminobenzoate Assembly by the Self-Sacrificial Heterobimetallic Protein CADD.
Excision of a Protein-Derived Amine for p-Aminobenzoate Assembly by the Self-Sacrificial Heterobimetallic Protein CADD.
复制标题
通过自我牺牲异双金属蛋白 CADD 切除用于对氨基苯甲酸酯组装的蛋白质衍生胺。
DOI：
10.1021/acs.biochem.3c00406
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发表时间：
2023
期刊：
影响因子：
2.9
通讯作者：
Makris,ThomasM
中科院分区：
文献类型：
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作者：
Phan,HanN;Manley,OliviaM;Skirboll,SydneyS;Cha,Lide;Hilovsky,Dalton;Chang,Wei-Chen;Thompson,PeterM;Liu,Xiaojing;Makris,ThomasM
衣原体死亡结构域相关蛋白（CADD）是最近发现的一类被称为血红素加氧酶样二甲氧化酶（HDOs）的非血红素二金属酶的创始人，在病原体生存中起着不可或缺的作用。CADD协调对氨基苯甲酸（pABA）的生物合成，通过自我牺牲的去除蛋白质衍生的酪氨酸（Tyr27）和几个额外的加工步骤整合到叶酸中，其性质和时间尚未完全澄清。核磁共振（NMR）和蛋白质组学方法揭示了邻近赖氨酸（Lys152）安装胺的来源和可能的时间。利用限制性o2进行的周转研究已经鉴定出对氨基苯甲醛（pABCHO）代谢中间体是在aba形成的途径上形成的。pabcho和其他探针底物的使用表明，该酶的异双金属Fe/Mn形式能够插入氧气生成paba -羧酸盐。
Chlamydia protein associating with death domains (CADD), the founding member of a recently discovered class of nonheme dimetal enzymes termed hemeoxygenase-like dimetaloxidases (HDOs), plays an indispensable role in pathogen survival. CADD orchestrates the biosynthesis ofp-aminobenzoic acid (pABA) for integration into folate via the self-sacrificial excision of a protein-derived tyrosine (Tyr27) and several additional processing steps, the nature and timing of which have yet to be fully clarified. Nuclear magnetic resonance (NMR) and proteomics approaches reveal the source and probable timing of amine installation by a neighboring lysine (Lys152). Turnover studies using limiting O2have identified apara-aminobenzaldehyde (pABCHO) metabolic intermediate that is formed on the path topABA formation. The use ofpABCHO and other probe substrates shows that the heterobimetallic Fe/Mn form of the enzyme is capable of oxygen insertion to generate the pABA-carboxylate.