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The functional and biological significance of selected CASP13 targets are described by the authors of the structures. The structural biologists discuss the most interesting structural features of the target proteins and assess whether these features were correctly reproduced in the predictions submitted to the CASP13 experiment.

Proton transfer from carbon enables an impressive array of racemizations, carboxylations, eliminations, isomerizations and carbon-carbon bond-forming reactions. Although such reactions often have considerable kinetic and thermodynamic barriers, the enzymes that [...], Linus Pauling established the conceptual framework for understanding and mimicking enzymes more than six decades ago (1). The notion that enzymes selectively stabilize the rate-limiting transition state of the catalysed reaction relative to the bound ground state reduces the problem of design to one of molecular recognition. Nevertheless, past attempts to capitalize on this idea, for example by using transition state analogues to elicit antibodies with catalytic activities (2), have generally failed to deliver true enzymatic rates. The advent of computational design approaches, combined with directed evolution, has provided an opportunity to revisit this problem. Starting from a computationally designed catalyst for the Kemp elimination (3)--a well-studied model system for proton transfer from carbon--we show that an artificial enzyme can be evolved that accelerates an elementary chemical reaction 6 X [10.sup.8]-fold, approaching the exceptional efficiency of highly optimized natural enzymes such as triosephosphate isomerase. A 1.09 Å resolution crystal structure of the evolved enzyme indicates that familiar catalytic strategies such as shape complementarity and precisely placed catalytic groups can be successfully harnessed to afford such high rate accelerations, making us optimistic about the prospects of designing more sophisticated catalysts.

Adiponectin has many beneficial effects on cardiovascularand obesity-relateddisorders. It is part of a class of proteins that contains short collagenousdomains, along with surfactant proteins A and D, and complement proteinC1q. This class of biomacromolecules requires post-translational modificationsto form biologically active assemblies. By introducing a set of post-translationalmodifying enzymes into Escherichia coli, we have created a prokaryotic expression system that functionallyassembles adiponectin, as assessed by the ability of produced adiponectinmultimers to suppress human endothelial cell apoptosis. This studyrepresents the first example of the assembly of functional high ordermultimers of any member of this class of proteins outside of eukaryoticcells. Furthermore, the results give fundamental insight into theprocess of assembly such as the necessity and sufficiency of variouspost-translational steps for functional assembly. We expect that fine-tuningof the expression system will allow for efficient production and functionalassembly of biomolecules that assemble via short collagenous domains. [ABSTRACT FROM AUTHOR]

A series of 2-amino-2,3-dihydro-1 H -indene-5-carboxamides were designed and synthesized as new selective discoidin domain receptor 1 (DDR1) inhibitors. One of the representative compounds, 7f , bound with DDR1 with a K d value of 5.9 nM and suppressed the kinase activity with an half-maximal (50%) inhibitory concentration value of 14.9 nM. 7f potently inhibited collagen-induced DDR1 signaling and epithelial-mesenchymal transition, dose-dependently suppressed colony formation of pancreatic cancer cells, and exhibited promising in vivo therapeutic efficacy in orthotopic mouse models of pancreatic cancer.