4gtr

FTase in complex with BMS analogue 13

spinqualitylabelsall models 4gtr, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4gtr is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 7TR, DMS, FPP, ZN Related: 4gtm, 4gto, 4gtp, 4gtq, 4gts, 4gtt, 4gtv Gene: Fnta (Buffalo rat), Fntb (Buffalo rat) Activity: Protein farnesyltransferase, with EC number 2.5.1.58 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [FNTA_RAT] Catalyzes the transfer of a farnesyl or geranyl-geranyl moiety from farnesyl or geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. The alpha subunit is thought to participate in a stable complex with the substrate. The beta subunit binds the peptide substrate. Through RAC1 prenylation and activation may positively regulate neuromuscular junction development downstream of MUSK (By similarity). [FNTB_RAT] Catalyzes the transfer of a farnesyl moiety from farnesyl pyrophosphate to a cysteine at the fourth position from the C-terminus of several proteins. The beta subunit is responsible for peptide-binding. Publication Abstract from PubMed Members of the Ras superfamily of small GTPases are frequently mutated in cancer. Therefore, inhibitors have been developed to address the acitivity of these GTPases by inhibiting their prenylating enzymes FTase, GGTase I, and RabGGTase. In contrast to FTase and GGTase I, only a handful of RabGGTase inhibitors have been developed. The most active RabGGTase inhibitor known until recently was an FTase inhibitor which hit RabGGTase as an off-target. We recently reported our efforts to tune the selectivity of these inhibitors toward RabGGTase. Here we describe an extended set of selective inhibitors. The requirements for selective RabGGTase inhibitors are described in detail, guided by multiple crystal structures. In order to relate in vitro and cellular activity, a high-throughput assay system to detect the attachment of [(3)H]geranylgeranyl groups to Rab was used. Selective RabGGTase inhibition allows the establishment of novel drug discovery programs aimed at the development of anticancer therapeutics. Development of Selective, Potent RabGGTase Inhibitors.,Stigter EA, Guo Z, Bon RS, Wu YW, Choidas A, Wolf A, Menninger S, Waldmann H, Blankenfeldt W, Goody RS J Med Chem. 2012 Oct 11;55(19):8330-40. doi: 10.1021/jm300624s. Epub 2012 Oct 3. PMID:22963166 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Farnesyltransferase

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