4GTS
Engineered RabGGTase in complex with BMS analogue 16
Summary for 4GTS
| Entry DOI | 10.2210/pdb4gts/pdb |
| Related | 4GTM 4GTO 4GTP 4GTQ 4GTR 4GTT 4GTV |
| Descriptor | Geranylgeranyl transferase type-2 subunit alpha, Geranylgeranyl transferase type-2 subunit beta, ZINC ION, ... (6 entities in total) |
| Functional Keywords | protein prenylation, inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Rattus norvegicus (rat) More |
| Total number of polymer chains | 2 |
| Total formula weight | 75782.60 |
| Authors | Guo, Z.,Stigter, E.A.,Bon, R.S.,Waldmann, H.,Blankenfeldt, W.,Goody, R.S. (deposition date: 2012-08-29, release date: 2012-10-24, Last modification date: 2023-11-08) |
| Primary citation | Stigter, E.A.,Guo, Z.,Bon, R.S.,Wu, Y.W.,Choidas, A.,Wolf, A.,Menninger, S.,Waldmann, H.,Blankenfeldt, W.,Goody, R.S. Development of Selective, Potent RabGGTase Inhibitors J.Med.Chem., 55:8330-8340, 2012 Cited by PubMed Abstract: 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. PubMed: 22963166DOI: 10.1021/jm300624s PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.45 Å) |
Structure validation
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