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Full-Text Articles in Life Sciences
Drug-Resistant Hiv-1 Protease Regains Functional Dynamics Through Cleavage Site Coevolution, Nevra Ozer, Aysegul Ozen, Celia Schiffer, Turkan Haliloglu
Drug-Resistant Hiv-1 Protease Regains Functional Dynamics Through Cleavage Site Coevolution, Nevra Ozer, Aysegul Ozen, Celia Schiffer, Turkan Haliloglu
Celia A. Schiffer
Drug resistance is caused by mutations that change the balance of recognition favoring substrate cleavage over inhibitor binding. Here, a structural dynamics perspective of the regained wild-type functioning in mutant HIV-1 proteases with coevolution of the natural substrates is provided. The collective dynamics of mutant structures of the protease bound to p1-p6 and NC-p1 substrates are assessed using the Anisotropic Network Model (ANM). The drug-induced protease mutations perturb the mechanistically crucial hinge axes that involve key sites for substrate binding and dimerization and mainly coordinate the intrinsic dynamics. Yet with substrate coevolution, while the wild-type dynamic behavior is restored in …
The Orientation Of Strophomenid Brachiopods On Soft Substrates, Roy Plotnick, Benjamin Dattilo, Daniel Piquard, Jennifer Bauer, Joshua Corrie
The Orientation Of Strophomenid Brachiopods On Soft Substrates, Roy Plotnick, Benjamin Dattilo, Daniel Piquard, Jennifer Bauer, Joshua Corrie
Benjamin F. Dattilo
Strophomenid brachiopods have long been interpreted as ‘‘snowshoe’’ strategists, with their flattened concavoconvex valves providing resistance to foundering in very soft sediments. There has been a sharp difference of opinion in whether the shells were oriented with their convex or their concave surface in contact with the sediment. This study, along with independent evidence from sedimentology, ichnology, and morphology, indicates that the strophomenids lived with their shells concave down (convex up). Experiments indicate the force required to push shells into soft cohesive muds is much greater for the convex up than for the convex down orientation. Forces also increase with …