6CDX
High-resolution crystal structure of fluoropropylated cystine knot, binding to alpha-5 beta-6 integrin
Summary for 6CDX
| Entry DOI | 10.2210/pdb6cdx/pdb |
| Related | 2N8B 2N8C |
| Descriptor | cystine knot (fluoropropylated) (2 entities in total) |
| Functional Keywords | cysteine, disulfides, alpha-5 beta-6 integrin binding epitope, cancer imaging, protein binding |
| Biological source | Momordica cochinchinensis (Spiny bitter cucumber) More |
| Total number of polymer chains | 2 |
| Total formula weight | 7833.00 |
| Authors | Kimura, R.,Nix, J.,Bongura, C.,Chakraborti, S.,Gambhir, S.,Filipp, F.V. (deposition date: 2018-02-09, release date: 2019-08-14, Last modification date: 2024-10-23) |
| Primary citation | Kimura, R.H.,Wang, L.,Shen, B.,Huo, L.,Tummers, W.,Filipp, F.V.,Guo, H.H.,Haywood, T.,Abou-Elkacem, L.,Baratto, L.,Habte, F.,Devulapally, R.,Witney, T.H.,Cheng, Y.,Tikole, S.,Chakraborti, S.,Nix, J.,Bonagura, C.A.,Hatami, N.,Mooney, J.J.,Desai, T.,Turner, S.,Gaster, R.S.,Otte, A.,Visser, B.C.,Poultsides, G.A.,Norton, J.,Park, W.,Stolowitz, M.,Lau, K.,Yang, E.,Natarajan, A.,Ilovich, O.,Srinivas, S.,Srinivasan, A.,Paulmurugan, R.,Willmann, J.,Chin, F.T.,Cheng, Z.,Iagaru, A.,Li, F.,Gambhir, S.S. Evaluation of integrin alpha v beta6cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis. Nat Commun, 10:4673-4673, 2019 Cited by PubMed Abstract: 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 αvβ 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 αβ. PubMed: 31611594DOI: 10.1038/s41467-019-11863-w PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1 Å) |
Structure validation
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