[HTML][HTML] Structural basis for bisphosphonate-mediated inhibition of isoprenoid biosynthesis
DJ Hosfield, Y Zhang, DR Dougan, A Broun… - Journal of Biological …, 2004 - ASBMB
Farnesyl pyrophosphate synthetase (FPPS) synthesizes farnesyl pyrophosphate through
successive condensations of isopentyl pyrophosphate with dimethylallyl pyrophosphate and
geranyl pyrophosphate. Nitrogen-containing bisphosphonate drugs used to treat osteoclast-
mediated bone resorption and tumor-induced hypercalcemia are potent inhibitors of the
enzyme. Here we present crystal structures of substrate and bisphosphonate complexes of
FPPS. The structures reveal how enzyme conformational changes organize conserved …
successive condensations of isopentyl pyrophosphate with dimethylallyl pyrophosphate and
geranyl pyrophosphate. Nitrogen-containing bisphosphonate drugs used to treat osteoclast-
mediated bone resorption and tumor-induced hypercalcemia are potent inhibitors of the
enzyme. Here we present crystal structures of substrate and bisphosphonate complexes of
FPPS. The structures reveal how enzyme conformational changes organize conserved …