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Silvia Armenta Silvia Moreno‐Mendieta Zaira Sánchez‐Cuapio Sergio Sánchez Romina Rodríguez‐Sanoja 《Proteins》2017,85(9):1602-1617
Carbohydrate‐binding modules (CBMs) are non‐catalytic domains that are generally appended to carbohydrate‐active enzymes. CBMs have a broadly conserved structure that allows recognition of a notable variety of carbohydrates, in both their soluble and insoluble forms, as well as in their alpha and beta conformations and with different types of bonds or substitutions. This versatility suggests a high functional plasticity that is not yet clearly understood, in spite of the important number of studies relating protein structure and function. Several studies have explored the flexibility of these systems by changing or improving their specificity toward substrates of interest. In this review, we examine the molecular strategies used to identify CBMs with novel or improved characteristics. The impact of the spatial arrangement of the functional amino acids of CBMs is discussed in terms of unexpected new functions that are not related to the original biological roles of the enzymes. Proteins 2017; 85:1602–1617. © 2017 Wiley Periodicals, Inc. 相似文献
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Joshua Lowrey Roberto E. Armenta Marianne S. Brooks 《Applied microbiology and biotechnology》2016,100(3):1061-1075
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Inès J Goossens-Beumer Jan Oosting Wim E Corver Marjolein JFW Janssen Bart Janssen Wilbert van Workum Eliane CM Zeestraten Cornelis JH van de Velde Hans Morreau Peter JK Kuppen Tom van Wezel 《BMC genomics》2015,16(1)
Background
In rectal cancer, total mesorectal excision surgery combined with preoperative (chemo)radiotherapy reduces local recurrence rates but does not improve overall patient survival, a result that may be due to the harmful side effects and/or co-morbidity of preoperative treatment. New biomarkers are needed to facilitate identification of rectal cancer patients at high risk for local recurrent disease. This would allow for preoperative (chemo)radiotherapy to be restricted to high-risk patients, thereby reducing overtreatment and allowing personalized treatment protocols. We analyzed genome-wide DNA copy number (CN) and allelic alterations in 112 tumors from preoperatively untreated rectal cancer patients. Sixty-six patients with local and/or distant recurrent disease were compared to matched controls without recurrence. Results were validated in a second cohort of tumors from 95 matched rectal cancer patients. Additionally, we performed a meta-analysis that included 42 studies reporting on CN alterations in colorectal cancer and compared results to our own data.Results
The genomic profiles in our study were comparable to other rectal cancer studies. Results of the meta-analysis supported the hypothesis that colon cancer and rectal cancer may be distinct disease entities. In our discovery patient study cohort, allelic retention of chromosome 7 was significantly associated with local recurrent disease. Data from the validation cohort were supportive, albeit not statistically significant, of this finding.Conclusions
We showed that retention of heterozygosity on chromosome 7 may be associated with local recurrence in rectal cancer. Further research is warranted to elucidate the mechanisms and effect of retention of chromosome 7 on the development of local recurrent disease in rectal cancer.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1550-0) contains supplementary material, which is available to authorized users. 相似文献35.
Studies of the hyaluronan (HA) tetrasaccharides are important for
understanding hydrogen-bonding in the HA polymer, as they are probably the
smallest oligomers in which characteristics of the constituent
monosaccharides and the polymer are simultaneously exhibited. Here we
present extensive molecular dynamics simulations of the two
tetrasaccharides of HA in dilute aqueous solution. These simulations have
confirmed the existence of intramolecular hydrogen-bonds between the
neighboring sugar residues of HA in solution, as proposed by Scott (1989).
However, our simulations predict that these intramolecular hydrogen-bonds
are not static as previously proposed, but are in constant dynamic exchange
on the sub-nanosecond time-scale. This process results in discrete internal
motion of the HA tetrasaccharides where they rapidly move between low
energy conformations. Specific interactions between water and
intramolecular hydrogen-bonds involving the hydroxymethyl group were found
to result in differing conformations and dynamics for the two alternative
tetrasaccharides of HA. This new observation suggests that this residue may
play a key role in the entropy and stability of HA in solution, allowing it
to stay soluble up to high concentration. The vicinal coupling constants3 J
NHCH of the acetamido groups have been calculated from our aqueous
simulations of HA. We found that high values of 3J NHCH approximately 8 Hz,
as experimentally measured for HA, are consistent with mixtures of both
trans and cis conformations, and thus3 J NHCH cannot be used to imply a
purely trans conformation of the acetamido. The rapid exchange of
intramolecular hydrogen-bonds indicates that although the structure is at
any moment stabilized by these hydrogen-bonds, no one hydrogen-bond exists
for an extended period of time. This could explain why NMR often fails to
provide evidence for intramolecular hydrogen-bonds in HA and other aqueous
carbohydrate structures.
相似文献
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Weifeng Liu Zachary Maben Carole Wang Kevin C. Lindquist Manqing Li Vinayak Rayannavar Ilsel Lopez Armenta Andrew Nager Edward Pascua Pawel K. Dominik David Oyen Hui Wang Rachel Carson Roach Corey M. Allan Lidia Mosyak Javier Chaparro-Riggers 《The Journal of biological chemistry》2021,297(4)
CD27 is a tumor necrosis factor (TNF) receptor, which stimulates lymphocytes and promotes their differentiation upon activation by TNF ligand CD70. Activation of the CD27 receptor provides a costimulatory signal to promote T cell, B cell, and NK cell activity to facilitate antitumor and anti-infection immunity. Aberrant increased and focused expression of CD70 on many tumor cells renders CD70 an attractive therapeutic target for direct tumor killing. However, despite their use as drug targets to treat cancers, the molecular basis and atomic details of CD27 and CD70 interaction remain elusive. Here we report the crystal structure of human CD27 in complex with human CD70. Analysis of our structure shows that CD70 adopts a classical TNF ligand homotrimeric assembly to engage CD27 receptors in a 3:3 stoichiometry. By combining structural and rational mutagenesis data with reported disease-correlated mutations, we identified the key amino acid residues of CD27 and CD70 that control this interaction. We also report increased potency for plate-bound CD70 constructs compared with solution-phase ligand in a functional activity to stimulate T-cells in vitro. These findings offer new mechanistic insight into this critical costimulatory interaction. 相似文献
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A new highly sensitive nonseparation enzyme immunoassay for human serum ferritin is described. Reagents include a beta-galactosidase-ferritin conjugate, sheep anti-ferritin, anti-sheep IgG, and dextran-linked beta-galactosylumbelliferone as enzyme substrate. The method is based on inhibition of enzyme activity when anti-ferritin binds to the enzyme-ferritin conjugate. Ferritin in the sample and enzyme-labeled ferritin compete for a limited quantity of anti-ferritin. The enzyme activity of the reaction mixture is directly related to the ferritin content of the sample. Some patients' samples caused strong interference in the assay due to the presence of antibody to beta-galactosidase. Several ways of eliminating the interference are presented. When measures were adopted to suppress sample interference, the assay results correlated well with those of other immunoassay methods. 相似文献
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