Tyrosine kinase receptor

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spinqualitylabelsall models Human TRK-A kinase domain complex with inhibitor, MPD and sulfate (PDB code 6p11) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Disease 3 Relevance 4 Structural highlights Function Tyrosine kinase receptor or high affinity nerve growth factor receptor (TRK-A) play an important role in cellular processes like growth, motility, differentiation and metabolism[1]. Disease Disregulation of TRK-A signalling leads to cancer. Relevance TRK-A inhibitors are suitable alternatives to teatment of neoendocrine tumors like pheochromocytomas and [2]. Structural highlights TRK-A contains an extracellular ligand binding domain (LBD), a transmembrane helix and an intracellular region which contains the kinase domain. The kinase domain (PDB code 4yne} contains the tripeptide DFG which flips out in TRK-A inactivated form. The structure of the complex of TRK-A with the phenylpyrrolidine derivative shows the inhibitor forming hydrogen bonds to Met620 and Lys572 residues and π-π interactions of it with Phe617 and Phe 698 [3].

3D Structures tyrosine kinase receptor

Updated on 30-March-2020

• Tyrosine kinase receptor or high affinity nerve growth factor receptor; Domains – extracellular 36-382; LBD 285-380; transmembrane 410-447; kinase 498-796

1he7 – hTRK-A LBD domain – human
4crp – hTRK-A LBD domain (mutant) – NMR
2ifg – hTRK-A extracellular domain + b-nerve growth factor
4gt5, 4f0i] – hTRK-A kinase domain
5kvt, 6pl1, 6npt, 6nsp, 6nss, 5wr7, 6d1y, 6d1z, 6pmc, 6iqn, 6pl2, 6pl3, 6pma, 6pmb, 6pme, 5kmj, 5kmk, 5kmm, 5kmn, 5kmo, 4aoj, 4pmm, 4pmp, 4pms, 4pmt, 4yps, 5h3q, 5i8a, 5kmi, 5kml, 6d20, 6dkb, 6dkg, 6dki, 6j5l, 5jfs, 5jfv, 5jfw, 5jfx, 4yne, 6dkw – hTRK-A kinase domain + inhibitor
2n90 – hTRK-A transmembrane domain - NMR

References

1. ↑ Du Z, Lovly CM. Mechanisms of receptor tyrosine kinase activation in cancer. Mol Cancer. 2018 Feb 19;17(1):58. doi: 10.1186/s12943-018-0782-4. PMID:29455648 doi:http://dx.doi.org/10.1186/s12943-018-0782-4
2. ↑ Cassol CA, Winer D, Liu W, Guo M, Ezzat S, Asa SL. Tyrosine kinase receptors as molecular targets in pheochromocytomas and paragangliomas. Mod Pathol. 2014 Aug;27(8):1050-62. doi: 10.1038/modpathol.2013.233. Epub 2014, Jan 3. PMID:24390213 doi:http://dx.doi.org/10.1038/modpathol.2013.233
3. ↑ Choi HS, Rucker PV, Wang Z, Fan Y, Albaugh P, Chopiuk G, Gessier F, Sun F, Adrian F, Liu G, Hood T, Li N, Jia Y, Che J, McCormack S, Li A, Li J, Steffy A, Culazzo A, Tompkins C, Phung V, Kreusch A, Lu M, Hu B, Chaudhary A, Prashad M, Tuntland T, Liu B, Harris J, Seidel HM, Loren J, Molteni V. (R)-2-Phenylpyrrolidine Substituted Imidazopyridazines: A New Class of Potent and Selective Pan-TRK Inhibitors. ACS Med Chem Lett. 2015 Mar 16;6(5):562-7. doi: 10.1021/acsmedchemlett.5b00050., eCollection 2015 May 14. PMID:26005534 doi:http://dx.doi.org/10.1021/acsmedchemlett.5b00050