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Crystal structure of zinc-substituted copper amine oxidase of Hansenula polymorpha expressed in Escherichia coli has been determined to 2.5-angstrom resolution. Copper amine oxidases (CAOs), using two cofactors, catalyze the two-electron oxidation of primary amines to aldehydes. The cofactors are a mononuclear copper and a unique redox cofactor. Molecular oxygen is used as a terminal electron acceptor. Rearrangement of other active site residues are proposed to be involved in binding of molecular oxygen. That may give information about how CAOs efficiently use their active site to carry out both cofactor formation and catalysis. The precursor tyrosine directly ligands the metal in the closest analogue so far of an intermediate in 2,4,5-trihydroxyphenylalanine quinone (TPQ) production.

Flavin reactivity and active site binding determinants have been studied relative to monomeric sarcosine oxidase (MSOX). Thermodynamic and spectroscopic properties of MSOX are described. X-ray crystallographic characterization of three new enzyme-inhibitor complexes has been carried out.

Research has been conducted on the Saccharomyces cerevisiae flavocytochrome b (sub)2. The investigation of the crystal structure of the yeast enzyme has been carried out.

The molecular aspects of interprotein complex-dependent change in the redox potential of amicyanin were investigated. It was found that this effect can be largely attributed to the significant pH reduction of the pK(subscript a) value of lower amounts of amicyanin as a result of complex formation with the quinoprotein methylamine dehydrogenase. Thus, it can be concluded that protein-protein interactions substantially affect the redox characteristics of type I copper protein amicyanin by restricting a pH-dependent, redox-based conformational change of one of the copper ligands.

Salusin-α is a bioactive peptide that protects against atherosclerosis and hepatosteatosis. Serum salusin-α level is declined in patients suffering with renal insufficiency. However, it is still undefined whether salusin-α plays a role in diabetic nephropathy. The present study was designed to investigate the potential roles of salusin-α in diabetic renal disease. Herein, we demonstrated that the salusin-α levels in both plasma and kidney tissues from diabetic rats were obviously downregulated. Exogenous administration of salusin-α eliminated the typical characteristics of diabetic nephropathy. Salusin-α treatment decreased renal fibrosis, which was related with reduced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. Injection of salusin-α suppressed the production of reactive oxygen species (ROS) via attenuation of NADPH oxidase subunits protein expressions and recovery of the antioxidant system. Mechanistically, the activated Akt/mTORC1/p70S6K signaling pathway in diabetic nephropathy was counteracted by salusin-α treatment. Our results demonstrated that salusin-α exerted protective effect against diabetic nephropathy via reduced oxidative stress and fibrosis, dependent on inactivation of the Akt/mTORC1/p70S6K signaling cascade. Salusin-α may be considered as a promising target for the treatment of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

The multiple isomorphous replacement method helps establish the crystal structure of recombinant bovine inositol polyphosphate 1-phosphatase (1-ptase), in the presence of Mg2+ at a resolution of 2.3 angstroms. 1-ptase exhibits monomerism and is alternatively folded into alpha/beta layers. The central core has a six-stranded antiparallel beta sheet with two perpendicular alpha-helices. Two antiparallel alpha-helices surround the beta sheet, while a five-stranded parallel beta sheet surrounds the central helices. The acidic pockets of the structure consist of two metal binding sites.

Abstract Background This study was designed to establish a biomarker risk model for predicting bone metastasis in stage III non-small cell lung cancer (NSCLC). Methods The model consists of 105 cases of stage III NSCLC, who were treated and followed up. The patients were divided into bone metastasis group (n = 45) and non-bone metastasis group (other visceral metastasis and those without recurrence) (n = 60). Tissue microarrays were constructed for immunohistochemical study of 10 molecular markers associated with bone metastasis, based on which a model was established via logistic regression analysis for predicting the risk of bone metastases. The model was prospectively validated in another 40 patients with stage III NSCLC. Results The molecular model for predicting bone metastasis was logit (P) = − 2.538 + 2.808 CXCR4 +1.629 BSP +0.846 OPN-2.939 BMP4. ROC test showed that when P ≥ 0.408, the sensitivity was up to 71% and specificity of 70%. Model validation in the 40 cases in clinical trial (NCT 01124253) demonstrated that the prediction sensitivity of the model was 85.7%, specificity 66.7%, Kappa: 0.618, with a high degree of consistency. Conclusion The molecular model combining CXCR4, BSP, OPN and BMP4 could help predict the risk of bone metastasis in stage IIIa and IIIb resected NSCLC.