6cdx

High-resolution crystal structure of fluoropropylated cystine knot, binding to alpha-5 beta-6 integrinHigh-resolution crystal structure of fluoropropylated cystine knot, binding to alpha-5 beta-6 integrin

Structural highlights 6cdx is a 2 chain structure with sequence from Momordica cochinchinensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ITR1_MOMCO Inhibits trypsin; probably participates in a plant defense mechanism. Publication Abstract from PubMed Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin alphavbeta6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer's safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin alphavbeta6. Evaluation of integrin alphavbeta6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis.,Kimura RH, Wang L, Shen B, Huo L, Tummers W, Filipp FV, Guo HH, Haywood T, Abou-Elkacem L, Baratto L, Habte F, Devulapally R, Witney TH, Cheng Y, Tikole S, Chakraborti S, Nix J, Bonagura CA, Hatami N, Mooney JJ, Desai T, Turner S, Gaster RS, Otte A, Visser BC, Poultsides GA, Norton J, Park W, Stolowitz M, Lau K, Yang E, Natarajan A, Ilovich O, Srinivas S, Srinivasan A, Paulmurugan R, Willmann J, Chin FT, Cheng Z, Iagaru A, Li F, Gambhir SS Nat Commun. 2019 Oct 14;10(1):4673. doi: 10.1038/s41467-019-11863-w. PMID:31611594 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 6cdx, resolution 1.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image