2Z50
S. cerevisiae geranylgeranyl pyrophosphate synthase in complex with BPH-28
Summary for 2Z50
| Entry DOI | 10.2210/pdb2z50/pdb |
| Related | 2Z4V 2Z4W 2Z4X 2Z4Y 2Z4Z 2Z52 |
| Descriptor | Geranylgeranyl pyrophosphate synthetase, (1-HYDROXYHEPTANE-1,1-DIYL)BIS(PHOSPHONIC ACID) (3 entities in total) |
| Functional Keywords | prenyltransferase, geranylgeranyl pyrophosphate, bisphosphonate, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Saccharomyces cerevisiae (Baker's yeast) |
| Cellular location | Cytoplasm (By similarity): Q12051 |
| Total number of polymer chains | 2 |
| Total formula weight | 79150.44 |
| Authors | Guo, R.T.,Chen, C.K.-M.,Hudock, M.,Cao, R.,Oldfield, E.,Wang, A.H.-J. (deposition date: 2007-06-26, release date: 2008-07-01, Last modification date: 2023-11-01) |
| Primary citation | Chen, C.K.-M.,Hudock, M.P.,Zhang, Y.,Guo, R.-T.,Cao, R.,No, J.H.,Liang, P.-H.,Ko, T.-P.,Chang, T.-H.,Chang, S.-C.,Song, Y.,Axelson, J.,Kumar, A.,Wang, A.H.-J.,Oldfield, E. Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation J.Med.Chem., 51:5594-5607, 2008 Cited by PubMed Abstract: We report the X-ray structures of several bisphosphonate inhibitors of geranylgeranyl diphosphate synthase, a target for anticancer drugs. Bisphosphonates containing unbranched side chains bind to either the farnesyl diphosphate (FPP) substrate site, the geranylgeranyl diphosphate (GGPP) product site, and in one case, both sites, with the bisphosphonate moiety interacting with 3 Mg (2+) that occupy the same position as found in FPP synthase. However, each of three "V-shaped" bisphosphonates bind to both the FPP and GGPP sites. Using the Glide program, we reproduced the binding modes of 10 bisphosphonates with an rms error of 1.3 A. Activities of the bisphosphonates in GGPPS inhibition were predicted with an overall error of 2x by using a comparative molecular similarity analysis based on a docked-structure alignment. These results show that some GGPPS inhibitors can occupy both substrate and product site and that binding modes as well as activity can be accurately predicted, facilitating the further development of GGPPS inhibitors as anticancer agents. PubMed: 18800762DOI: 10.1021/jm800325y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.01 Å) |
Structure validation
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