5uut | pdb_00005uut

N-myristoyltransferase 1 (NMT) bound to myristoyl-CoA

spinqualitylabelsall models 5uut, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5uut is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CIT, MYA Gene: NMT1, NMT (HUMAN) Activity: Glycylpeptide N-tetradecanoyltransferase, with EC number 2.3.1.97 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [NMT1_HUMAN] Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins. Publication Abstract from PubMed Protein N-myristoylation enables localization to membranes and helps maintain protein conformation and function. N-myristoyltransferases (NMT) catalyze co- or posttranslational myristoylation of Src family kinases and other oncogenic proteins, thereby regulating their function. In this study, we provide genetic and pharmacologic evidence that inhibiting the N-myristoyltransferase NMT1 suppresses cell-cycle progression, proliferation, and malignant growth of prostate cancer cells. Loss of myristoylation abolished the tumorigenic potential of Src and its synergy with androgen receptor in mediating tumor invasion. We identified the myristoyl-CoA analogue B13 as a small-molecule inhibitor of NMT1 enzymatic activity. B13 exposure blocked Src myristoylation and Src localization to the cytoplasmic membrane, attenuating Src-mediated oncogenic signaling. B13 exerted its anti-invasive and antitumor effects against prostate cancer cells, with minimal toxic side-effects in vivo Structural optimization based on structure-activity relationships enabled the chemical synthesis of LCL204, with enhanced inhibitory potency against NMT1. Collectively, our results offer a preclinical proof of concept for the use of protein myristoylation inhibitors as a strategy to block prostate cancer progression. Cancer Res; 77(24); 6950-62. (c)2017 AACR. Blocking Myristoylation of Src Inhibits Its Kinase Activity and Suppresses Prostate Cancer Progression.,Kim S, Alsaidan OA, Goodwin O, Li Q, Sulejmani E, Han Z, Bai A, Albers T, Beharry Z, Zheng YG, Norris JS, Szulc ZM, Bielawska A, Lebedyeva I, Pegan SD, Cai H Cancer Res. 2017 Dec 15;77(24):6950-6962. doi: 10.1158/0008-5472.CAN-17-0981., Epub 2017 Oct 16. PMID:29038344 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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