The structure of VibH represents nonribosomal peptide synthetase condensation, cyclization and epimerization domains
The structure of VibH represents nonribosomal peptide synthetase condensation, cyclization and epimerization domains
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DOI：
10.1038/nsb810
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发表时间：
2002-07-01
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影响因子：
--
通讯作者：
Keating, AE
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文献类型：
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作者：
Keating, TA;Marshall, CG;Keating, AE
非核糖体肽合成酶（NRPS）是一种大的，多结构域的酶，生物合成医学上重要的天然产物。我们报告的晶体结构的独立NRPS缩合（C）结构域VibH，它催化酰胺键的形成在合成的弧菌，霍乱弧菌铁载体。尽管低序列同一性，NRPS缩合酶在结构上与氯霉素乙酰转移酶（CAT）和二氢硫辛酰胺酰基转移酶相关。然而，尽管后一种酶是同三聚体，但VibH是单体假二聚体。VibH结构代表NRPS缩合和差向异构化结构域，以及缩合变体环化结构域，它们都预期是单体。令人惊讶的是，尽管有利的定位在活性位点，一个普遍保守的组氨酸在CAT和其他C结构域中的重要性是不关键的VibH中的一般碱催化。
Nonribosomal peptide synthetases (NRPSs) are large, multidomain enzymes that biosynthesize medically important natural products. We report the crystal structure of the freestanding NRPS condensation (C) domain VibH, which catalyzes amide bond formation in the synthesis of vibriobactin, a Vibrio cholerae siderophore. Despite low sequence identity, NRPS condensation enzymes are structurally related to chloramphenicol acetyltransferase (CAT) and dihydrolipoamide acyltransferases. However, although the latter enzymes are homotrimers, VibH is a monomeric pseudodimer. The VibH structure is representative of both NRPS condensation and epimerization domains, as well as the condensation-variant cyclization domains, which are all expected to be monomers. Surprisingly, despite favorable positioning in the active site, a universally conserved histidine important in CAT and in other C domains is not critical for general base catalysis in VibH.