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Molecular Biology Commons

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Selected Works

2016

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Articles 31 - 32 of 32

Full-Text Articles in Molecular Biology

Structural And Thermodynamic Effects Of Macrocyclization In Hcv Ns3/4a Inhibitor Mk-5172, Djade Soumana, Nese Yilmaz, Kristina Prachanronarong, Cihan Aydin, Akbar Ali, Celia Schiffer Jan 2016

Structural And Thermodynamic Effects Of Macrocyclization In Hcv Ns3/4a Inhibitor Mk-5172, Djade Soumana, Nese Yilmaz, Kristina Prachanronarong, Cihan Aydin, Akbar Ali, Celia Schiffer

Celia A. Schiffer

Recent advances in direct-acting antivirals against Hepatitis C Virus (HCV) have led to the development of potent inhibitors, including MK-5172, that target the viral NS3/4A protease with relatively low susceptibility to resistance. MK-5172 has a P2-P4 macrocycle and a unique binding mode among current protease inhibitors where the P2 quinoxaline packs against the catalytic residues H57 and D81. However, the effect of macrocyclization on this binding mode is not clear, as is the relation between macrocyclization, thermodynamic stabilization, and susceptibility to the resistance mutation A156T. We have determined high-resolution crystal structures of linear and P1-P3 macrocyclic analogs of MK-5172 bound …


Testing The Metabolic Theory Of Ecology., Andrew Kerkhoff Jan 2016

Testing The Metabolic Theory Of Ecology., Andrew Kerkhoff

Andrew J Kerkhoff

The metabolic theory of ecology (MTE) predicts the effects of body size and temperature on metabolism through considerations of vascular distribution networks and biochemical kinetics. MTE has also been extended to characterise processes from cellular to global levels. MTE has generated both enthusiasm and controversy across a broad range of research areas. However, most efforts that claim to validate or invalidate MTE have focused on testing predictions. We argue that critical evaluation of MTE also requires strong tests of both its theoretical foundations and simplifying assumptions. To this end, we synthesise available information and find that MTE's original derivations require …