5yjm

Human chymase in complex with 7-oxo-3-(phenoxyimino)-1,4-diazepane derivative

spinqualitylabelsall models 5yjm, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5yjm is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: 8W3, NAG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CMA1_HUMAN Major secreted protease of mast cells with suspected roles in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion. Publication Abstract from PubMed Based on insight from the X-ray crystal structure of human chymase in complex with compound 1, a lactam carbonyl of the diazepane core was exchanged with O-substituted oxyimino group, leading to amidoxime derivatives. This modification resulted in highly potent chymase inhibitors, such as O-phenylamidoxime 5f. X-ray crystal structure analysis indicated that compound 5f induced movement of the Leu99 and Tyr94 side chains at the S2 site, and the increase in inhibitory activity of O-phenyl amidoxime derivatives suggested that the O-phenyl moiety interacted with the Tyr94 residue. Surface plasmon resonance experiments showed that compound 5f had slower association and dissociation kinetics and the calculated residence time of compound 5f to human chymase was extended compared to that of amide compound 1. Structure-based design, synthesis, and binding mode analysis of novel and potent chymase inhibitors.,Futamura-Takahashi J, Tanaka T, Sugawara H, Iwashita S, Imajo S, Oyama Y, Muto T Bioorg Med Chem Lett. 2018 Jan 15;28(2):188-192. doi: 10.1016/j.bmcl.2017.11.031., Epub 2017 Nov 16. PMID:29191554 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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