The crystal structures of both Nova KH3 domains are similar to the previously determined NMR structures. The most significant differences among the KH domains involve changes in the positioning of one or more of the alpha helices with respect to the betasheet, particularly in the NMR structure of the KH1 domain of the Fragile X disease protein FMR-1. Loop regions in the KH domains are clearly visible in the crystal structure, unlike the NMR structures, revealing the conformation of the invariant Gly-X-X-Gly segment that is thought to participate in RNA-binding and of the variable region. The tetrameric arrangements of the Nova KH3 domains provide insights into how KH domains may interact with each other in proteins containing multiple KH motifs.

The structure of a Nova protein K homology (KH) domain recognizing single-stranded RNA has been determined at 2.4 A resolution. Mammalian Nova antigens (1 and 2) constitute an important family of regulators of RNA metabolism in neurons, first identified using sera from cancer patients with the autoimmune disorder paraneoplastic opsoclonus-myoclonus ataxia (POMA). The structure of the third KH domain (KH3) of Nova-2 bound to a stem loop RNA resembles a molecular vise, with 5'-Ura-Cyt-Ade-Cyt-3' pinioned between an invariant Gly-X-X-Gly motif and the variable loop. Tetranucleotide recognition is supported by an aliphatic alpha helix/beta sheet RNA-binding platform, which mimics 5'-Ura-Gua-3' by making Watson-Crick-like hydrogen bonds with 5'-Cyt-Ade-3'. Sequence conservation suggests that fragile X mental retardation results from perturbation of RNA binding by the FMR1 protein.

X-ray structures of two enzymes in the sterol͞isoprenoid biosynthesis pathway have been determined in a structural genomics pilot study. Mevalonate-5-diphosphate decarboxylase (MDD) is a single-domain ␣͞␤ protein that catalyzes the last of three sequential ATP-dependent reactions which convert mevalonate to isopentenyl diphosphate. Isopentenyl disphosphate isomerase (IDI) is an ␣͞␤ metalloenzyme that catalyzes interconversion of isopentenyl diphosphate and dimethylallyl diphosphate, which condense in the next step toward synthesis of sterols and a host of natural products. Homology modeling of related proteins and comparisons of the MDD and IDI structures with two other experimentally determined structures have shown that MDD is a member of the GHMP superfamily of small-molecule kinases and IDI is similar to the nudix hydrolases, which act on nucleotide diphosphatecontaining substrates. Structural models were produced for 379 proteins, encompassing a substantial fraction of both protein superfamilies. All three enzymes responsible for synthesis of isopentenyl diphosphate from mevalonate (mevalonate kinase, phosphomevalonate kinase, and MDD) share the same fold, catalyze phosphorylation of chemically similar substrates (MDD decarboxylation involves phosphorylation of mevalonate diphosphate), and seem to have evolved from a common ancestor. These structures and the structural models derived from them provide a framework for interpreting biochemical function and evolutionary relationships.H igh-throughput genome sequencing has dramatically expanded our knowledge of the proteins of the natural world. Next steps in understanding these macromolecules will involve studies of biochemical and biological function, depending critically on three-dimensional structural information. Nascent structural genomics efforts are aimed at developing experimental and computational pipelines for studying protein structure and integrating their results into the mainstream of biomedical research (1).

In higher education, micro-credentials – that is, proof of the learning results a student has acquired after a short learning programme (SLP) – are gaining in importance. In general, SLPs are formative programs addressed to professionals in a specific area of knowledge. Despite the various characteristics of this type of training, delivered in a wide range of teaching centres and modalities, and therefore the difficulties in defining it, this article presents the first experience of a recognised external quality assurance agency of higher education in accrediting these programs under the European Qualifications Framework (EQF) and European Standards and Guidelines for Quality Assurance in the European Higher Education Area (ESGs). This is a pioneering experience in Europe, which also has the active and direct participation of universities, the professional sector and government departments (specifically those responsible for university, continuous education and employment policies). From an initial assessment of 33 SLPs, organised by universities and aligned with the demands of the productive sector, different conclusions are drawn. The validity of the proposed evaluation methodology, focused on eight specific dimensions, is emphasised, but there are also difficulties inherent in this type of assessment, such as the qualifications of students who access the programs and the balance between the academic and professional characteristics of the teachers concerned.