These NMR results accompanying with visible absorption spectroscopy and visible resonance Raman spectroscopy reveal that oxy-Hb in the presence of L35 and IHP below pH 7 takes the ligated T-quaternary structure under the P(O2) of 760 mmHg. The L35-concentration NU7026 dependence of the T-marker in the presence of IHP indicates that there are more

than one kind of L35-binding sites in the ligated T-quaternary structure. The stronger binding sites are probably intra-dimeric binding sites between alpha(1)G- and beta(1)G-helices, and the other weaker binding site causes the R -> T transition without release of O(2). The fluctuation of the tertiary structure of Hb seems to be caused by both the structural perturbation of alpha(1)beta(1) (or alpha(2)beta(2)) intra-dimeric interface, where the stronger L35-binding sites exist, and by the IHP-binding to the alpha(1)alpha(2)-

(or beta(1)beta(2)-) cavity. The tertiary structural fluctuation induced by the allosteric effectors may contribute to the significant reduction of the O(2)-affinity of oxy-Hb, which little depends on the quaternary structures. Therefore, the widely held assumptions of the structure-function correlation of Hb – [the deoxy-state] = [the T-quaternary structure] = [the low O(2)-affinity state] and [the oxy-state] = [the R-quaternary structure] = [the high O(2)-affinity state] and the O(2)-affiny of Hb being regulated by the T/R-quaternary structural transition – are no longer sustainable. This article is part of Compound C in vivo a Special Issue entitled: Allosteric cooperativity in respiratory proteins. (C) 2011 selleck Published by Elsevier B.V.”
“Multidrug resistance (MDR) remains a significant problem for effective cancer chemotherapy. In spite of considerable advances in drug discovery, most of the cancer

cases still stay incurable because of resistance to chemotherapy. We synthesized a novel, Mn (II) complex (chelate), viz., manganese N-(2-hydroxy acetophenone) glycinate (MnNG) that exhibits considerable efficacy to overcome drug resistant cancer. The antiproliferative activity of MnNG was studied on doxorubicin resistant and sensitive human T lymphoblastic leukemia cells (CEM/ADR 5000 and CCRF/CEM). MnNG induced apoptosis significantly in CEM/ADR 5000 cells probably through generation of reactive oxygen species. Moreover, intraperitoneal (i:p.) application of MnNG at non-toxic doses caused significant increase in the life-span of Swiss albino mice bearing sensitive and doxorubicin resistant subline of Ehrlich ascites carcinoma cells. (C) 2013 Elsevier B.V. All rights reserved.”
“West Nile virus capsid protein (WNVCp) displays pathogenic toxicity via the apoptotic pathway. However, a cellular mechanism protective against this toxic effect has not been observed so far. Here, we identified Makorin ring finger protein 1 (MKRN1) as a novel E3 ubiquitin ligase for WNVCp.