The endless subtleties of RNA-protein complexes

New NMR structures of complexes between double-strand RNA binding domains and their RNA hairpin substrates reported by Wang et?al. in this issue of Structure reveal striking adaptations in both the protein recognition element and in the RNA.     

One-shot reciprocity under error management is unbiased and fragile

The error management model of altruism in one-shot interactions provides an influential explanation for one of the most controversial behaviors in evolutionary social science. The model posits that one-shot altruism arises from a domain-specific cognitive bias that avoids the error of mistaking a long-term relationship for a one-shot interaction. One-shot altruism is thus, in an intriguingly paradoxical way, a form of reciprocity. We examine the logic behind this idea in detail. In its most general form the error management model is exceedingly flexible, and restrictions about the psychology of agents are necessary for selection to be well-defined. Once these restrictions are in place, selection is well defined, but it leads to behavior that is perfectly consistent with an unbiased rational benchmark. Thus, the evolution of one-shot reciprocity does not require an evoked cognitive bias based on repeated interactions and reputation. Moreover, in spite of its flexibility in terms of psychology, the error management model assumes that behavior is exceedingly rigid when individuals face a new interaction partner. Reciprocity can only take the form of tit-for-tat, and individuals cannot adjust their behavior in response to new information about the duration of a relationship. Zefferman (2014) showed that one-shot reciprocity does not reliably evolve if one relaxes the first restriction, and we show that the behavior does not reliably evolve if one relaxes the second restriction. Altogether, these theoretical results on one-shot reciprocity do not square well with experiments showing increased altruism in the presence of payoff-irrelevant stimuli that suggest others are watching.     

Atomic resolution crystal structures and quantum chemistry meet to reveal subtleties of hydroxynitrile lyase catalysis

Hydroxynitrile lyases are versatile enzymes that enantiospecifically cope with cyanohydrins, important intermediates in the production of various agrochemicals or pharmaceuticals. We determined four atomic resolution crystal structures of hydroxynitrile lyase from Hevea brasiliensis: one native and three complexes with acetone, isopropyl alcohol, and thiocyanate. We observed distinct distance changes among the active site residues related to proton shifts upon substrate binding. The combined use of crystallography and ab initio quantum chemical calculations allowed the determination of the protonation states in the enzyme active site. We show that His(235) of the catalytic triad must be protonated in order for catalysis to proceed, and we could reproduce the cyanohydrin synthesis in ab initio calculations. We also found evidence for the considerable pK(a) shifts that had been hypothesized earlier. We envision that this knowledge can be used to enhance the catalytic properties and the stability of the enzyme for industrial production of enantiomerically pure cyanohydrins.     

The enantiomeric error frequency of aspartate aminotransferase

The enantiomeric error frequency of aspartate aminotransferase (mitochondrial isoenzyme from chicken) was assessed by adding the enzyme in high concentration (0.89 mM) to a mixture of L-glutamate and 2-oxoglutarate (12 and 1.2 mM, respectively, at pH 7.5 and 25 degrees C). The substrates continuously undergo the transamination cycle under these conditions. Thereby, L-glutamate is progressively racemized, a 1:1 ratio of two enantiomers being reached within 240 h. The enantiomeric error frequency, i.e. the ratio of the rate of D-glutamate production and the rate of the transamination reaction with glutamate and 2-oxoglutarate as substrates, is 1.5 x 10(-7). D-Glutamate is also converted to a 1:1 racemic mixture. The racemizing activity of a mixture of free pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate is about two orders of magnitude lower than that of aspartate aminotransferase. The error frequency of the enzyme in the case of the C4 substrate pair aspartate and oxalacetate is 3.4 x 10(-8), i.e. 4 times lower than that with the C5 substrate pair.