Serum Albumin: A Multifaced Enzyme De Simone, Giovanna; di Masi, Alessandra; Ascenzi, Paolo
International journal of molecular sciences,
09/2021, Letnik:
22, Številka:
18
Journal Article
Recenzirano
Odprti dostop
Human serum albumin (HSA) is the most abundant protein in plasma, contributing actively to oncotic pressure maintenance and fluid distribution between body compartments. HSA acts as the main carrier ...of fatty acids, recognizes metal ions, affects pharmacokinetics of many drugs, provides the metabolic modification of some ligands, renders potential toxins harmless, accounts for most of the anti-oxidant capacity of human plasma, and displays esterase, enolase, glucuronidase, and peroxidase (pseudo)-enzymatic activities. HSA-based catalysis is physiologically relevant, affecting the metabolism of endogenous and exogenous compounds including proteins, lipids, cholesterol, reactive oxygen species (ROS), and drugs. Catalytic properties of HSA are modulated by allosteric effectors, competitive inhibitors, chemical modifications, pathological conditions, and aging. HSA displays anti-oxidant properties and is critical for plasma detoxification from toxic agents and for pro-drugs activation. The enzymatic properties of HSA can be also exploited by chemical industries as a scaffold to produce libraries of catalysts with improved proficiency and stereoselectivity for water decontamination from poisonous agents and environmental contaminants, in the so called “green chemistry” field. Here, an overview of the intrinsic and metal dependent (pseudo-)enzymatic properties of HSA is reported to highlight the roles played by this multifaced protein.
For refugees and immigrants in the United States, expressions of citizenship and belonging emerge not only during the naturalization process but also during more informal, everyday activities in the ...community. Based on research in the Dallas–Arlington–Fort Worth area of Texas, this book examines the sociocultural spaces in which Vietnamese and Indian immigrants are engaging with the wider civic sphere.As Civic Engagements reveals, religious and ethnic organizations provide arenas in which immigrants develop their own ways of being and becoming "American." Skills honed at a meeting, festival, or banquet have resounding implications for the future political potential of these immigrant populations, both locally and nationally. Employing Lave and Wenger's concept of "communities of practice" as a framework, this book emphasizes the variety of processes by which new citizens acquire the civic and leadership skills that help them to move from peripheral positions to more central roles in American society.
Binding of the vasodilator peptides adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) to the class B G protein-coupled receptor calcitonin receptor-like receptor (CLR) is modulated by ...receptor activity-modifying proteins (RAMPs). RAMP1 favors CGRP, whereas RAMP2 and RAMP3 favor AM. Crystal structures of peptide-bound RAMP1/2-CLR extracellular domain (ECD) heterodimers suggested RAMPs alter ligand preference through direct peptide contacts and allosteric modulation of CLR. Here, we probed this dual mechanism through rational structure-guided design of AM and CGRP antagonist variants. Variants were characterized for binding to purified RAMP1/2-CLR ECD and for antagonism of the full-length CGRP (RAMP1:CLR), AM
(RAMP2:CLR), and AM
(RAMP3:CLR) receptors. Short nanomolar affinity AM(37-52) and CGRP(27-37) variants were obtained through substitutions including AM S45W/Q50W and CGRP K35W/A36S designed to stabilize their
-turn. K46L and Y52F substitutions designed to exploit RAMP allosteric effects and direct peptide contacts, respectively, yielded AM variants with selectivity for the CGRP receptor over the AM
receptor. AM(37-52) S45W/K46L/Q50W/Y52F exhibited nanomolar potency at the CGRP receptor and micromolar potency at AM
A 2.8-Å resolution crystal structure of this variant bound to the RAMP1-CLR ECD confirmed that it bound as designed. CGRP(27-37) N31D/S34P/K35W/A36S exhibited potency and selectivity comparable to the traditional antagonist CGRP(8-37). Giving this variant the ability to contact RAMP2 through the F37Y substitution increased affinity for AM
, but it still preferred the CGRP receptor. These potent peptide antagonists with altered selectivity inform the development of AM/CGRP-based pharmacological tools and support the hypothesis that RAMPs alter CLR ligand selectivity through allosteric effects and direct peptide contacts.
The other alliance Klimke, Martin
2010, 2010., 20091221, 2009, 2010-01-01, 20100101, Letnik:
7
eBook, Book
SDS meets SDS -- Between Berkeley and Berlin, Frankfurt and San Francisco : the networks and nexus of transnational protest -- Building the second front : the transatlantic antiwar alliance -- Black ...and red panthers -- The other alliance and the transatlantic partnership -- Student protest and international relations.
A Youth Compendium of Physical Activities (Youth Compendium) was developed to estimate the energy costs of physical activities using data on youth only.
On the basis of a literature search and pooled ...data of energy expenditure measurements in youth, the energy costs of 196 activities were compiled in 16 activity categories to form a Youth Compendium of Physical Activities. To estimate the intensity of each activity, measured oxygen consumption (V˙O2) was divided by basal metabolic rate (Schofield age-, sex-, and mass-specific equations) to produce a youth MET (METy). A mixed linear model was developed for each activity category to impute missing values for age ranges with no observations for a specific activity.
This Youth Compendium consists of METy values for 196 specific activities classified into 16 major categories for four age-groups, 6-9, 10-12, 13-15, and 16-18 yr. METy values in this Youth Compendium were measured (51%) or imputed (49%) from youth data.
This Youth Compendium of Physical Activities uses pediatric data exclusively, addresses the age dependency of METy, and imputes missing METy values and thus represents advancement in physical activity research and practice. This Youth Compendium will be a valuable resource for stakeholders interested in evaluating interventions, programs, and policies designed to assess and encourage physical activity in youth.
QSAR without borders Muratov, Eugene N; Bajorath, Jürgen; Sheridan, Robert P ...
Chemical Society reviews,
06/2020, Letnik:
49, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Prediction of chemical bioactivity and physical properties has been one of the most important applications of statistical and more recently, machine learning and artificial intelligence methods in ...chemical sciences. This field of research, broadly known as quantitative structure-activity relationships (QSAR) modeling, has developed many important algorithms and has found a broad range of applications in physical organic and medicinal chemistry in the past 55+ years. This Perspective summarizes recent technological advances in QSAR modeling but it also highlights the applicability of algorithms, modeling methods, and validation practices developed in QSAR to a wide range of research areas outside of traditional QSAR boundaries including synthesis planning, nanotechnology, materials science, biomaterials, and clinical informatics. As modern research methods generate rapidly increasing amounts of data, the knowledge of robust data-driven modelling methods professed within the QSAR field can become essential for scientists working both within and outside of chemical research. We hope that this contribution highlighting the generalizable components of QSAR modeling will serve to address this challenge.
Background and Purpose
Receptor activity‐modifying proteins (RAMPs) define the pharmacology of the calcitonin receptor‐like receptor (CLR). The interactions of the different RAMPs with this class B ...GPCR yield high‐affinity calcitonin gene‐related peptide (CGRP) or adrenomedullin (AM) receptors. However, the mechanism for this is unclear.
Experimental Approach
Guided by receptor models, we mutated residues in the N‐terminal helix of CLR, RAMP2 and RAMP3 hypothesized to be involved in peptide interactions. These were assayed for cAMP production with AM, AM2 and CGRP together with their cell surface expression. Binding studies were also conducted for selected mutants.
Key Results
An important domain for peptide interactions on CLR from I32 to I52 was defined. Although I41 was universally important for binding and receptor function, the role of other residues depended on both ligand and RAMP. Peptide binding to CLR/RAMP3 involved a more restricted range of residues than that to CLR/RAMP1 or CLR/RAMP2. E101 of RAMP2 had a major role in AM interactions, and F111/W84 of RAMP2/3 was important with each peptide.
Conclusions and Implications
RAMP‐dependent effects of CLR mutations suggest that the different RAMPs control accessibility of peptides to binding residues situated on the CLR N‐terminus. RAMP3 appears to alter the role of specific residues at the CLR‐RAMP interface compared with RAMP1 and RAMP2.
Enzyme activity as a method for soil biochemistry and microbiology research has a long history of more than 100 years that is not widely acknowledged in terms of adherence to strict assay protocols ...and the interpretation of results. However, in the recent past, there is a growing lack of recognition of the historic advancements among researchers that use soil enzymology. Today, many papers are being published that use methods that either do not follow exact protocols as originally vetted in the research literature or individual labs use their own method that has not been optimized for pH, co-factors, substrate concentrations, or other conditions. This is of particular concern for fluorogenic substrates and microplate methods. Furthermore, there is a lack of understanding of the origin and location of a given enzyme being studied. Notably, regardless of the enzyme, it is too often assumed that enzyme activity equals microbial activity—which is not the case for most hydrolytic enzyme assays. Because as established by Douglas McLaren in the 1950s, a considerable amount of activity can come from catalytic enzymes stabilized in the soil matrix but that are no longer associated with viable cells (known as abiontic enzymes). In summary, today, many papers are using imperfect methods and/or misinterpret enzyme activity data that at a minimum confounds cross paper studies and meta-analysis. However, most importantly, lack of historical perspectives and ignoring strict protocols cause redundancy and fundamentally undermine the discipline and understanding of soil microbiology/biochemistry when enzymology methods are used.
Marine Drugs is very pleased to host a Special Issue in honour of Prof. Dr. Peter Proksch, who served as Editor in Chief for Marine Drugs from 2005 to 2009, for his excellent research contribution.
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