The DJ-1 gene encodes a ubiquitous, highly conserved protein. Here, we show that DJ-1 mutations are associated with PARK7, a monogenic form of human parkinsonism. The function of the DJ-1 protein remains unknown, but evidence suggests its involvement in the oxidative stress response. Our findings indicate that loss of DJ-1 function leads to neurodegeneration. Elucidating the physiological role of DJ-1 protein may promote understanding of the mechanisms of brain neuronal maintenance and pathogenesis of Parkinson's disease.

https://science.sciencemag.org/content/sci/299/5604/256.full.pdf

Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism

ACPYPE (or AnteChamber PYthon Parser interfacE) is a wrapper script around the ANTECHAMBER software that simplifies the generation of small molecule topologies and parameters for a variety of molecular dynamics programmes like GROMACS, CHARMM and CNS. It is written in the Python programming language and was developed as a tool for interfacing with other Python based applications such as the CCPN software suite (for NMR data analysis) and ARIA (for structure calculations from NMR data). ACPYPE is open source code, under GNU GPL v3, and is available as a stand-alone application at http://www.ccpn.ac.uk/acpype
 and as a web portal application at http://webapps.ccpn.ac.uk/acpype
 . We verified the topologies generated by ACPYPE in three ways: by comparing with default AMBER topologies for standard amino acids; by generating and verifying topologies for a large set of ligands from the PDB; and by recalculating the structures for 5 protein–ligand complexes from the PDB. ACPYPE is a tool that simplifies the automatic generation of topology and parameters in different formats for different molecular mechanics programmes, including calculation of partial charges, while being object oriented for integration with other applications.

https://link.springer.com/content/pdf/10.1186%2F1756-0500-5-367.pdf

ACPYPE - AnteChamber PYthon Parser interfacE

SUMMARY Strains of bacteria resistant to antibiotics, particularly those that are multiresistant, are an increasing major health care problem around the world. It is now abundantly clear that both Gram-negative and Gram-positive bacteria are able to meet the evolutionary challenge of combating antimicrobial chemotherapy, often by acquiring preexisting resistance determinants from the bacterial gene pool. This is achieved through the concerted activities of mobile genetic elements able to move within or between DNA molecules, which include insertion sequences, transposons, and gene cassettes/integrons, and those that are able to transfer between bacterial cells, such as plasmids and integrative conjugative elements. Together these elements play a central role in facilitating horizontal genetic exchange and therefore promote the acquisition and spread of resistance genes. This review aims to outline the characteristics of the major types of mobile genetic elements involved in acquisition and spread of antibiotic resistance in both Gram-negative and Gram-positive bacteria, focusing on the so-called ESKAPEE group of organisms (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli), which have become the most problematic hospital pathogens.

https://cmr.asm.org/content/cmr/31/4/e00088-17.full-text.pdf

Mobile Genetic Elements Associated with Antimicrobial Resistance

A correct alignment is an essential requirement in homology modeling. Yet in order to bridge the structural gap between template and target, which may not only involve loop rearrangements, but also shifts of secondary structure elements and repacking of core residues, high-resolution refinement methods with full atomic details are needed. Here, we describe four approaches that address this "last mile of the protein folding problem" and have performed well during CASP8, yielding physically realistic models: YASARA, which runs molecular dynamics simulations of models in explicit solvent, using a new partly knowledge-based all atom force field derived from Amber, whose parameters have been optimized to minimize the damage done to protein crystal structures. The LEE-SERVER, which makes extensive use of conformational space annealing to create alignments, to help Modeller build physically realistic models while satisfying input restraints from templates and CHARMM stereochemistry, and to remodel the side-chains. ROSETTA, whose high resolution refinement protocol combines a physically realistic all atom force field with Monte Carlo minimization to allow the large conformational space to be sampled quickly. And finally UNDERTAKER, which creates a pool of candidate models from various templates and then optimizes them with an adaptive genetic algorithm, using a primarily empirical cost function that does not include bond angle, bond length, or other physics-like terms.

Improving physical realism, stereochemistry, and side-chain accuracy in homology modeling: Four approaches that performed well in CASP8.

The Protein Data Bank (PDB) is the world-wide repository of macromolecular structure information. We present a series of databases that run parallel to the PDB. Each database holds one entry, if possible, for each PDB entry. DSSP holds the secondary structure of the proteins. PDBREPORT holds reports on the structure quality and lists errors. HSSP holds a multiple sequence alignment for all proteins. The PDBFINDER holds easy to parse summaries of the PDB file content, augmented with essentials from the other systems. PDB_REDO holds re-refined, and often improved, copies of all structures solved by X-ray. WHY_NOT summarizes why certain files could not be produced. All these systems are updated weekly. The data sets can be used for the analysis of properties of protein structures in areas ranging from structural genomics, to cancer biology and protein design.

/pdf/a-series-of-pdb-related-databases-for-everyday-needs-31gfx8ffvy.pdf

A series of PDB related databases for everyday needs.

One of the conclusions drawn at the CASP4 meeting in Asilomar was that applying various force fields during refinement of template-based models tends to move predictions in the wrong direction, away from the experimentally determined coordinates. We have derived an all-atom force field aimed at protein and nucleotide optimization in vacuo (NOVA), which has been specifically designed to avoid this problem. NOVA resembles common molecular dynamics force fields but has been automatically parameterized with two major goals: (i) not to make high resolution X-ray structures worse and (ii) to improve homology models built by WHAT IF. Force-field parameters were not required to be physically correct; instead, they were optimized with random Monte Carlo moves in force-field parameter space, each one evaluated by simulated annealing runs of a 50-protein optimization set. Errors inherent to the approximate force-field equation could thus be canceled by errors in force-field parameters. Compared with the optimization set, the force field did equally well on an independent validation set and is shown to move in silico models closer to reality. It can be applied to modeling applications as well as X-ray and NMR structure refinement. A new method to assign force-field parameters based on molecular trees is also presented. A NOVA server is freely accessible at http://www.yasara.com/servers

/pdf/increasing-the-precision-of-comparative-models-with-yasara-5498p4h0qt.pdf

Increasing the precision of comparative models with YASARA NOVA--a self-parameterizing force field.

The cell wall of Gram-negative bacteria is essential for the integrity of the bacterial cell but also imposes a physical barrier to trans-envelope transport processes in which DNA and/or proteins are taken up or secreted by complex protein assemblies. The presence of genes encoding lytic transglycosylases in macromolecular transport systems (bacteriophage entry, type II secretion and type IV pilus synthesis, type III secretion, type IV secretion) suggests an important role for these specialised cell-wall-degrading enzymes. Such enzymes are capable of locally enlarging gaps in the peptidoglycan meshwork to allow the efficient assembly and anchoring of supramolecular transport complexes in the cell envelope. In this review, current knowledge on the role and distribution of these specialised murein-degrading enzymes in diverse macromolecular transport systems is summarised and discussed.

Lytic transglycosylases in macromolecular transport systems of Gram-negative bacteria.

Advances in concrete materials for sewer systems affected by microbial induced concrete corrosion: A review.

Conjugative plasmids are involved in the dissemination of important traits such as antibiotic resistance, virulence determinants and metabolic pathways involved in adapting to environmental niches, a process termed horizontal or lateral gene transfer. Conjugation is the process of transferring DNA from a donor to a recipient cell with the establishment of the incoming DNA and its cargo of genetic traits within the transconjugant. Conjugation is mediated by self-transmissible plasmids as well as phage-like sequences that have been integrated into the bacterial chromosome, such as integrative and conjugative elements (ICEs) that now include conjugative transposons. Both conjugative plasmids and ICEs can mediate the transfer of mobilizable elements by sharing their conjugative machinery. Conjugation can either be induced, usually by small molecules or peptides or by excision of the ICE from the host chromosome, or it can be tightly regulated by plasmid- and host-encoded factors. The transfer potential of these transfer regions depends on the integration of many signals in response to environmental and physiological cues. This review will focus on the mechanisms that influence transfer potential in these systems, particularly those of the IncF incompatibility group.

Regulation of bacterial conjugation: balancing opportunity with adversity

Specialized lytic transglycosylases are muramidases capable of locally degrading the peptidoglycan meshwork of Gram-negative bacteria. Specialized lytic transglycosylase genes are present in clusters encoding diverse macromolecular transport systems. This paper reports the analysis of selected members of the specialized lytic transglycosylase family from type III and type IV secretion systems. These proteins were analysed in vivo by assaying their ability to complement the DNA transfer defect of the conjugative F-like plasmid R1-16 lacking a functional P19 protein, the specialized lytic transglycosylase of this type IV secretion system. Heterologous complementation was accomplished using IpgF from the plasmid-encoded type III secretion system of Shigella sonnei and TrbN from the type IV secretion system of the conjugative plasmid RP4. In contrast, neither VirB1 proteins (Agrobacterium tumefaciens, Brucella suis) nor IagB (Salmonella enterica) could functionally replace P19. In vitro, IpgF, IagB, both VirB1 proteins, HP0523 (Helicobacter pylori) and P19 displayed peptidoglycanase activity in zymogram analyses. Using an established test system and a newly developed assay it was shown that IpgF degraded peptidoglycan in solution. IpgF was active only after removal of the chaperonin GroEL, which co-purified with IpgF and inhibited its enzymic activity. A mutant IpgF protein in which the predicted catalytic amino acid, Glu42, was replaced by Gln, was completely inactive. IpgF-catalysed peptidoglycan degradation was optimal at pH 6 and was inhibited by the lytic transglycosylase inhibitors hexa-N-acetylchitohexaose and bulgecin A.

Günther Koraimann

Papers

Increasing the precision of comparative models with YASARA NOVA--a self-parameterizing force field.

Lytic transglycosylases in macromolecular transport systems of Gram-negative bacteria.

Advances in concrete materials for sewer systems affected by microbial induced concrete corrosion: A review.

Regulation of bacterial conjugation: balancing opportunity with adversity

Peptidoglycan degradation by specialized lytic transglycosylases associated with type III and type IV secretion systems.