RCSB Protein Data Bank: visualizing groups of experimentally determined PDB structures alongside computed structure models of proteins

Recent advances in Artificial Intelligence and Machine Learning (e.g., AlphaFold, RosettaFold, and ESMFold) enable prediction of three-dimensional (3D) protein structures from amino acid sequences alone at accuracies comparable to lower-resolution experimental methods. These tools have been employed to predict structures across entire proteomes and the results of large-scale metagenomic sequence studies, yielding an exponential increase in available biomolecular 3D structural information. Given the enormous volume of this newly computed biostructure data, there is an urgent need for robust tools to manage, search, cluster, and visualize large collections of structures. Equally important is the capability to efficiently summarize and visualize metadata, biological/biochemical annotations, and structural features, particularly when working with vast numbers of protein structures of both experimental origin from the Protein Data Bank (PDB) and computationally-predicted models. Moreover, researchers require advanced visualization techniques that support interactive exploration of multiple sequences and structural alignments. This paper introduces a suite of tools provided on the RCSB PDB research-focused web portal RCSB. org, tailor-made for efficient management, search, organization, and visualization of this burgeoning corpus of 3D macromolecular structure data

X-ray structures of two proteins belonging to Pfam DUF178 revealed unexpected structural similarity to the DUF191 Pfam family

<p>Abstract</p> <p>Background</p> <p>Pfam is a comprehensive collection of protein domains and families, with a range of well-established information including genome annotation. Pfam has two large series of functionally uncharacterized families, known as Domains of Unknown Function (DUFs) and Uncharacterized Protein Families (UPFs).</p> <p>Results</p> <p>Crystal structures of two proteins from <it>Deinococcus radiodurans </it>and <it>Streptomyces coelicolor </it>belonging to Pfam protein family DUF178 (ID: PF02621) have been determined using Selenium-Single-wavelength Anomalous Dispersion (Se-SAD). Based on the structure, we have identified the putative function for this family of protein.</p> <p>Conclusion</p> <p>Unexpectedly, we found that DUF178 Pfam is remarkably similar to Pfam family DUF191 suggesting that the sequence-based classification alone may not be sufficient to classify proteins into Pfam families.</p

Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein

AbstractThe cocrystal structure of human poly(A)-binding protein (PABP) has been determined at 2.6 Å resolution. PABP recognizes the 3′ mRNA poly(A) tail and plays critical roles in eukaryotic translation initiation and mRNA stabilization/degradation. The minimal PABP used in this study consists of the N-terminal two RRM-type RNA-binding domains connected by a short linker (RRM1/2). These two RRMs form a continuous RNA-binding trough, lined by an antiparallel β sheet backed by four α helices. The polyadenylate RNA adopts an extended conformation running the length of the molecular trough. Adenine recognition is primarily mediated by contacts with conserved residues found in the RNP motifs of the two RRMs. The convex dorsum of RRM1/2 displays a phylogenetically conserved hydrophobic/acidic portion, which may interact with translation initiation factors and regulatory proteins

Structural basis for activation of the therapeutic l-nucleoside analogs 3TC and troxacitabine by human deoxycytidine kinase

l-nucleoside analogs represent an important class of small molecules for treating both viral infections and cancers. These pro-drugs achieve pharmacological activity only after enzyme-catalyzed conversion to their tri-phosphorylated forms. Herein, we report the crystal structures of human deoxycytidine kinase (dCK) in complex with the l-nucleosides (−)-β-2′,3′-dideoxy-3′-thiacytidine (3TC)—an approved anti-human immunodeficiency virus (HIV) agent—and troxacitabine (TRO)—an experimental anti-neoplastic agent. The first step in activating these agents is catalyzed by dCK. Our studies reveal how dCK, which normally catalyzes phosphorylation of the natural d-nucleosides, can efficiently phosphorylate substrates with non-physiologic chirality. The capability of dCK to phosphorylate both d- and l-nucleosides and nucleoside analogs derives from structural properties of both the enzyme and the substrates themselves. First, the nucleoside-binding site tolerates substrates with different chiral configurations by maintaining virtually all of the protein-ligand interactions responsible for productive substrate positioning. Second, the pseudo-symmetry of nucleosides and nucleoside analogs in combination with their conformational flexibility allows the l- and d-enantiomeric forms to adopt similar shapes when bound to the enzyme. This is the first analysis of the structural basis for activation of l-nucleoside analogs, providing further impetus for discovery and clinical development of new agents in this molecular class

The RCSB Protein Data Bank: views of structural biology for basic and applied research and education.

The RCSB Protein Data Bank (RCSB PDB, http://www.rcsb.org) provides access to 3D structures of biological macromolecules and is one of the leading resources in biology and biomedicine worldwide. Our efforts over the past 2 years focused on enabling a deeper understanding of structural biology and providing new structural views of biology that support both basic and applied research and education. Herein, we describe recently introduced data annotations including integration with external biological resources, such as gene and drug databases, new visualization tools and improved support for the mobile web. We also describe access to data files, web services and open access software components to enable software developers to more effectively mine the PDB archive and related annotations. Our efforts are aimed at expanding the role of 3D structure in understanding biology and medicine

Performance of the double multilayer monochromator on the NSLS wiggler beam line X25

A tunable, double multilayer x-ray monochromator has recently been implemented on the National Synchrotron Light Source (NSLS) X25 wiggler beam line. It is based on a parallel pair of tungsten-boron-carbide multilayer films grown on silicon substrates and purchased from Osmic, Inc. of Troy, Michigan, USA. It acts as an optional alternative to the conventional double silicon crystal monochromator, and uses the same alignment mechanism. Two other NSLS beam lines also have had this kind of monochromator installed recently, following the lead of the NSLS X20C IBM/MIT beam line which has used a double multilayer monochromator for several years. Owing to the 100 times broader bandwidth of a multilayer x-ray monochromator, compared with a silicon monochromator, the multilayer monochromator has the obvious advantage of delivering 100 times the flux of a silicon monochromator, and thereby makes more efficient use of the continuous synchrotron radiation spectrum, yet preserves the narrow collimation of the incident synchrotron beam. In particular, multilayer x-ray bandwidths, on the order of 1%, are well-matched to x-ray undulator linewidths. Performance results for the X25 multilayer monochromator are presented, comparing it with the silicon monochromator. Of note is its short- and long-term performance as an x-ray monochromator delivering the brightness of the wiggler source in the presence of the high-power white beam. Detailed measurements of its spatial beam profile and wavelength dispersion have been made, and it is shown how its resolution could be improved when desired. Finally, its peculiar, anisotropic resolution function in reciprocal space, and its bearing upon x-ray crystallography and scattering experiments, will be discussed, and highlighted by the results of a protein crystallography experiment. © 1997 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87844/2/71_1.pd