3HXB
Engineered RabGGTase in complex with a peptidomimetic inhibitor (compound 6)
Summary for 3HXB
| Entry DOI | 10.2210/pdb3hxb/pdb |
| Related | 3HXC 3HXD 3HXE 3HXF |
| Descriptor | Geranylgeranyl transferase type-2 subunit alpha, Geranylgeranyl transferase type-2 subunit beta, N-[(benzyloxy)carbonyl]-D-tyrosyl-L-phenylalanyl-L-tyrosine, ... (5 entities in total) |
| Functional Keywords | protein prenylation inhibition, metal-binding, prenyltransferase, transferase, zinc |
| Biological source | Rattus norvegicus (rat) More |
| Total number of polymer chains | 2 |
| Total formula weight | 76024.84 |
| Authors | Guo, Z.,Alexandrov, K.,Waldmann, H.,Goody, R.S.,Blankenfeldt, W. (deposition date: 2009-06-20, release date: 2009-09-08, Last modification date: 2023-09-06) |
| Primary citation | Tan, K.T.,Guiu-Rozas, E.,Bon, R.S.,Guo, Z.,Delon, C.,Wetzel, S.,Arndt, S.,Alexandrov, K.,Waldmann, H.,Goody, R.S.,Wu, Y.W.,Blankenfeldt, W. Design, synthesis, and characterization of Peptide-based rab geranylgeranyl transferase inhibitors J.Med.Chem., 52:8025-8037, 2009 Cited by PubMed Abstract: Rab geranylgeranyl transferase (RabGGTase) catalyzes the attachment of geranylgeranyl isoprenoids to Rab guanine triphosphatases, which are key regulators in vesicular transport. Because geranylgeranylation is required for proper function and overexpression of Rabs has been observed in various cancers, RabGGTase may be a target for novel therapeutics. The development of selective inhibitors is, however, difficult because two related enzymes involved in other cellular processes exist in eukaryotes and because RabGGTase recognizes protein substrates indirectly, resulting in relaxed specificity. We report the synthesis of a peptidic library based on the farnesyl transferase inhibitor pepticinnamin E. Of 469 compounds investigated, several were identified as selective for RabGGTase with low micromolar IC(50) values. The compounds were not generally cytotoxic and inhibited Rab isoprenylation in COS-7 cells. Crystal structure analysis revealed that selective inhibitors interact with a tunnel unique to RabGGTase, implying that this structural motif is an attractive target for improved RabGGTase inhibitors. PubMed: 19894725DOI: 10.1021/jm901117d PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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