Stephen J. Benkovic

[6] This was illustrated in his studies on dihydrofolate reductase (DHFR) that identified dynamic structural changes and their time scale that optimized the enzyme turnover.

[8][15] Significant changes in the rates of hydride transfer were not limited to active-site residues, nor were the effects of multiple mutations additive in terms of free energy.

[16] Genomic analysis of multiple DHFR sequences revealed low overall DNA sequence homology (30%), but surprisingly high conservation in the same regions whose amino acids had been implicated in catalysis by kinetic analysis, NMR measurements, and molecular dynamics simulations.

[6] The latter directly incorporated these distal residues into a network that acted along the reaction coordinate to facilitate the hydride transfer.

Only a small change triggered by movement within the protein fold along a network of coupled residues is needed to surmount the reaction barrier.

The T4 replisome can be assembled in vitro from eight separate proteins into the four units that catalyze leading and lagging strand synthesis at a replication fork.

[24] Spatial control of purinosome assembly in HeLa cells was found to be microtubule assisted and to colocalize with mitochondria as shown by super resolution chemical imaging.

Their low systemic toxicity in laboratory animals led to the founding of Anacor Pharmaceuticals by Benkovic and Lucy Shapiro that developed and commercialized nonsteroidal anti-inflammatory drug for pediatric and adult use.

[31] Continuing research suggests that boron containing molecules can have a potential to intervene in a variety of diseases such as—bacterial and fungal infections, pulmonary hypertension, and oncology.

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FGMAS GART
De Novo Purine Biosynthesis