Xanthomonas campestris PqqD in the pyrroloquinoline quinone biosynthesis operon adopts a novel saddle-like fold that possibly serves as a PQQ carrier
Xanthomonas campestris PqqD in the pyrroloquinoline quinone biosynthesis operon adopts a novel saddle-like fold that possibly serves as a PQQ carrier
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DOI：
10.1002/prot.22461
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发表时间：
2009-09-01
影响因子：
2.9
通讯作者：
Chou, Shan-Ho
中科院分区：
文献类型：
--
作者：
Tsai, Tung-Yi;Yang, Chao-Yu;Chou, Shan-Ho
Pyrroloquinoline quinone (4, 5-dihydro-4, 5-dioxo-1H-pyrrolo-[2, 3-f] quinoline-2, 7, 9-tricarboxylic acid, PQQ) is a novel heat-stable, water-soluble redox cofactor present in a variety of bacterial alcohol and aldose dehydrogenases. 1–5 It belongs to the third family of ortho-quinone cofactor following the well-known pyridine nucleotide-(such as NAD) and flavin-dependent (such as FAD) cofactors. 6, 7 However, PQQ is unique in that it can act either as an antioxidant or as a pro-oxidant, depending on the conditions of different biological systems. 8 Discovery of PQQ has also elicited considerable interests due to its role as a growth-promoting factor both in animals9 and plants. 10 Although the structures and functions of many enzymes using PQQ as a cofactor has been elucidated, 2–5, 11 relatively little is known about the pathway leading to the biosynthesis of this intriguing cofactor. However, some progresses have been made to date. For example, six genes belonging to the pqqABC-DEF operon were found to be essential for the biosynthesis of PQQ in Klebsiella pneumoniae. 12, 13 Of the six gene products, the first one (PqqA) is a 23-residue peptide with conserved glutamate and tyrosine residues that likely serves as the precursor for PQQ. 14–16 The second one (PqqB) is not directly involved in the PQQ biosynthesis12 but may serve as a carrier for PQQ when PQQ is released from PqqC. This is because PQQ can react with oxygen to generate deleterious free radicals when set free without protection. 17 Recently, the crystal structure of PqqB was released (PDB: 1XTO), which reveals a halfmoon shaped molecule comprising a metallo-hydrolase/oxidoreductase fold and a putative PQQ binding site near a zinc atom. However, a comprehensive functional assignment for PqqB has not been achieved. The third one (PqqC) is possibly the most studied protein in the pqq operon and has been demonstrated to catalyze the last step in the PQQ biosynthesis pathway. 18 Its tertiary structure has also been determined recently by X-ray crystallography (1OTV and 1OTW) and was found to adopt a homodimer, with each monomer folding into a compact seven helix bundle that provides a scaffold for the active site cavity. 18, 19 Upon substrate binding, PqqC was found to undergo large conformational changes. PqqC is also unique because it is an oxidase yet contains no redox active metal or other cofactor. The next component PqqE was found to catalyze a radical reaction link-
