Unique binding of a non-natural l,l,l-substrate by isopenicillin N synthase

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• 作者：Annaleise R. Howard-Jones ; Peter J. Rutledge ; Ian J. Clifton ; Robert M. Adlington and Jack E. Baldwin
• 关键词：Isopenicillin N synthase ; Penicillin biosynthesis ; Crystal structure ; l ; l ; l-Tripeptide ; Metalloenzyme ; Antibiotics
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：336
• 期：2
• 页码：702-708
• 全文大小：303 K

文摘

Isopenicillin N synthase (IPNS) is a non-haem iron oxidase that catalyses the formation of isopenicillin N from the tripeptide δ-(l-α-aminoadipoyl)-l-cysteinyl-d-valine. In this report, we describe the crystal structure of the enzyme with a non-natural l,l,l-tripeptide substrate, δ-(l-α-aminoadipoyl)-l-cysteinyl-l-3,3,3,3′,3′,3′-hexafluorovaline. This structure reveals a strong binding interaction of the tripeptide within the active site and a unique conformation for the non-natural l,l,l-diastereomer. Taken together, these findings provide a possible rationale for the previously observed inhibitory effects of l,l,l-tripeptide substrates on IPNS activity.