4QXS

Crystal structure of human FPPS in complex with WC01088

Summary for 4QXS

• Entry DOI: 10.2210/pdb4qxs/pdb
• Descriptor: Farnesyl pyrophosphate synthase, PHOSPHATE ION, (2-{2-[(2S)-3-methylbutan-2-yl]-5-phenyl-1H-indol-3-yl}ethane-1,1-diyl)bis(phosphonic acid), ... (5 entities in total)
• Functional Keywords: transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P14324
• Total number of polymer chains: 1
• Total formula weight: 43878.41

Authors

Park, J.,Zielinski, M.,Weiling, C.,Tsantrizos, Y.S.,Berghuis, A.M. (deposition date: 2014-07-21, release date: 2015-02-25, Last modification date: 2023-09-20)

Primary citation

Gritzalis, D.,Park, J.,Chiu, W.,Cho, H.,Lin, Y.S.,De Schutter, J.W.,Lacbay, C.M.,Zielinski, M.,Berghuis, A.M.,Tsantrizos, Y.S.
Probing the molecular and structural elements of ligands binding to the active site versus an allosteric pocket of the human farnesyl pyrophosphate synthase.
Bioorg.Med.Chem.Lett., 25:1117-1123, 2015

PubMed Abstract: In order to explore the interactions of bisphosphonate ligands with the active site and an allosteric pocket of the human farnesyl pyrophosphate synthase (hFPPS), substituted indole and azabenzimidazole bisphosphonates were designed as chameleon ligands. NMR and crystallographic studies revealed that these compounds can occupy both sub-pockets of the active site cavity, as well as the allosteric pocket of hFPPS in the presence of the enzyme's Mg(2+) ion cofactor. These results are consistent with the previously proposed hypothesis that the allosteric pocket of hFPPS, located near the active site, plays a feed-back regulatory role for this enzyme.

PubMed: 25630225
DOI: 10.1016/j.bmcl.2014.12.089

Experimental method

X-RAY DIFFRACTION (1.9 Å)