Unique binding of a non-natural L,L,L-substrate by isopenicillin N synthase.
Isopenicillin N synthase (IPNS) is a non-haem iron oxidase that catalyses the formation of isopenicillin N from the tripeptide delta-(L-alpha-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, delta-(L-alpha-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.
Howard-Jones
Annaleise R
AR
Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK. annaleise_howard-jones@hms.harvard.edu
Rutledge
Peter J
PJ
Clifton
Ian J
IJ
Adlington
Robert M
RM
Baldwin
Jack E
JE
D001665:Binding Sites; D003198:Computer Simulation; D004789:Enzyme Activation; D008956:Models, Chemical; D008958:Models, Molecular; D010088:Oxidoreductases / Q000032:analysis* / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D013379:Substrate Specificity
D010088:Oxidoreductases; C038370:isopenicillin N synthetase