The crystal structure of the C-terminal domain of the salmonella enterica pduo protein: An old fold with a new heme-binding mode

The two-domain protein PduO, involved in 1,2-propanediol utilization in the pathogenic Gram-negative bacterium Salmonella enterica is an ATP:Cob(I)alamin adenosyltransferase, but this is a function of the N-terminal domain alone. The role of its C-terminal domain (PduOC) is, however, unknown. In this study, comparative growth assays with a set of Salmonella mutant strains showed that this domain is necessary for effective in vivo catabolism of 1,2-propanediol. It was also shown that isolated, recombinantly-expressed PduOC binds heme in vivo. The structure of PduOC co-crystallized with heme was solved (1.9 \uc5 resolution) showing an octameric assembly with four heme moieities. The four heme groups are highly solvent-exposed and the heme iron is hexa-coordinated with bis-His ligation by histidines from different monomers. Static light scattering confirmed the octameric assembly in solution, but a mutation of the heme-coordinating histidine caused dissociation into dimers. Isothermal titration calorimetry using the PduOC apoprotein showed strong heme binding (Kd = 1.6 7 10 127 M). Biochemical experiments showed that the absence of the C-terminal domain in PduO did not affect adenosyltransferase activity in vitro. The evidence suggests that PduOC:heme plays an important role in the set of cobalamin transformations required for effective catabolism of 1,2-propanediol. Salmonella PduO is one of the rare proteins which binds the redox-active metabolites heme and cobalamin, and the heme-binding mode of the C-terminal domain differs from that in other members of this protein family

Propuesta de mejora al modelo de negocio de la empresa consultora GO-SCM para la implementaci?n de SAP IBP

La empresa consultora GO-SCM Chile es l?der en implementaci?n de SAP-IBP y est? orientada al segmento de grandes empresas con ingresos superiores a US$250 millones. Sin embargo, existen aspectos no desarrollados en cuanto a: 1) gesti?n de operaciones, que incluyen los procesos de la empresa, la metodolog?a de ejecuci?n de proyectos y la gesti?n del conocimiento; 2) gesti?n de recursos humanos, que permita la correcta selecci?n y evaluaci?n del equipo del proyecto, as? como evitar la rotaci?n de personal en especial por ser posiciones de alta especializaci?n; y 3) gesti?n de calidad, que oriente a la empresa hacia el cliente y eval?e constantemente su desempe?o y resultados. Con la finalidad de optimizar sus recursos, incrementar la rentabilidad y elevar el nivel de servicio al cliente, haci?ndola de esta manera m?s competitiva, se propone un modelo de negocio mejorado, formul?ndose para ello una metodolog?a de implementaci?n base y ?gil que puede ser adaptada a distintos escenarios o clientes, generando principalmente ahorros en los tiempos de ejecuci?n de los proyectos (desviaci?n actual: 49%) y elevando el nivel de servicio (NPS actual: -25%). As? mismo, se definieron los procesos empresariales, acciones para la gesti?n de los recursos y la gesti?n de calidad

Positive association of dopamine D2 receptor polymorphism with bipolar affective disorder in a European Multicenter Association Study of Affective Disorders

Convincing evidence for a genetic component in the etiology of affective disorders (AD), including bipolar affective disorder (BPAD) and unipolar affective disorder (UPAD), is supported by traditional and molecular genetic studies. Most arguments lead to the complex inheritance hypothesis, suggesting that the mode of inheritance is probably not Mendelian but most likely oligogenic (or polygenic) and that the contribution of genes could be moderate or weak. The purpose of the present European multicenter study (13 centers) was to test the potential role in BPAD and UPAD of two candidate dopaminergic markers, DRD2 and DRD3, using a case-control association design. The following samples were analyzed for DRD2: 358 BPAD/358 control (C) and 133 UPAD/ 133 C subjects, and for DRD3: 325 BPAD/ 325 C and 136 UPAD/136 C subjects. Patients and controls were individually matched for sex, age ( plus minus five years) and geographical origin. Evidence for significant association between BPAD and DRD2 emerged, with an over-representation of genotype 5-5 (P=0.004) and allele 5 (P=0.002) in BPAD cases compared to controls. No association was found for DRD2 in UPAD, and for DRD3 neither in BPAD or UPAD. Our results suggest that the DRD2 microsatellite may be in linkage disequilibrium with a nearby genetic variant involved in the susceptibility to BPAD. Our large European sample allowed for replicating of some previous reported positive findings obtained in other study populations.Journal ArticleMulticenter StudySCOPUS: ar.jinfo:eu-repo/semantics/publishe