1oyv
Crystal structure of tomato inhibitor-II in a ternary complex with subtilisin Carlsberg
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OverviewOverview
Multidomain proteinase inhibitors play critical roles in the defense of plants against predation by a wide range of pests. Despite a wealth of structural information on proteinase-single domain inhibitor interactions, the structural basis of inhibition by multidomain proteinase inhibitors remains poorly understood. Here we report the 2.5-A resolution crystal structure of the two-headed tomato inhibitor-II (TI-II) in complex with two molecules of subtilisin Carlsberg; it reveals how a multidomain inhibitor from the Potato II family of proteinase inhibitors can bind to and simultaneously inhibit two enzyme molecules within a single ternary complex. The N terminus of TI-II initiates the folding of Domain I (Lys-1 to Cys-15 and Pro-84 to Met-123) and then completes Domain II (Ile-26 to Pro-74) before coming back to complete the rest of Domain I (Pro-84 to Met-123). The two domains of TI-II adopt a similar fold and are arranged in an extended configuration that presents two reactive site loops at the opposite ends of the inhibitor molecule. Each subtilisin molecule interacts with a reactive site loop of TI-II through the standard, canonical binding mode. Remarkably, a significant distortion of the active site of subtilisin is induced by the presence of phenylalanine in the P1 position of reactive site loop II of TI-II. The structure of the TI-II.(subtilisin)2 complex provides a molecular framework for understanding how multiple inhibitory domains in a single Potato II type proteinase inhibitor molecule from the Potato II family act to inhibit proteolytic enzymes.
About this StructureAbout this Structure
1OYV is a Protein complex structure of sequences from Bacillus licheniformis and Solanum lycopersicum with as ligand. Active as Subtilisin, with EC number 3.4.21.62 Full crystallographic information is available from OCA.
ReferenceReference
Structural basis of inhibition revealed by a 1:2 complex of the two-headed tomato inhibitor-II and subtilisin Carlsberg., Barrette-Ng IH, Ng KK, Cherney MM, Pearce G, Ryan CA, James MN, J Biol Chem. 2003 Jun 27;278(26):24062-71. Epub 2003 Apr 8. PMID:12684499
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