4hgc

Crystal structure of bovine trypsin complexed with sfti-1 analog containing a peptoid residue at position p1

spinqualitylabelsall models 4hgc, resolution 1.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hgc is a 2 chain structure with sequence from Bos taurus and Helianthus annuus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.29Å Ligands: CA, GOL, NLY, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRY1_BOVIN Publication Abstract from PubMed Peptide-peptoid hybrids are found to be potent inhibitors of serine proteases. These engineered peptidomimetics benefit from both types of units of the biopolymeric structure: the natural inhibitor part serves as a good binding template, while the P1-positioned peptoid component provides complete resistance towards proteolysis. In this report, the mechanism of proteolytic resistance of a P1 peptoid-containing analogue is postulated based on the crystal structure of the (NLys)(5)-modified sunflower trypsin inhibitor SFTI-1 in complex with bovine trypsin solved at 1.29 A resolution. The structural differences between the (NLys)(5)SFTI-1-trypsin complex and the native SFTI-1-trypsin complex are surprisingly small and reveal the key role of the carbonyl group of the Ser214 residue of the enzyme, which is crucial for binding of the inhibitor and plays a crucial role in proteolysis mediated by serine proteases. The incorporated NLys5 peptoid residue prevents Ser214 from forming a hydrogen bond to the P1 residue, and in turn Gln192 does not form a hydrogen bond to the carbonyl group of the P2 residue. It also increases the distance between the Ser214 carbonyl group and the Ser195 residue, thus preventing proteolysis. The hybrid inhibitor structure reported here provides insight into protein-protein interaction, which can be efficiently and selectively probed with the use of peptoids incorporated within endogenous peptide ligands. Structure of a proteolytically resistant analogue of (NLys)(5)SFTI-1 in complex with trypsin: evidence for the direct participation of the Ser214 carbonyl group in serine protease-mediated proteolysis.,Krzywda S, Jaskolski M, Rolka K, Stawikowski MJ Acta Crystallogr D Biol Crystallogr. 2014 Mar;70(Pt 3):668-75. doi:, 10.1107/S1399004713032252. Epub 2014 Feb 15. PMID:24598736 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Trypsin 3D structures Trypsin inhibitor 3D structures

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