Here we show that scavenger receptor class B type I is present in the small-intestine brush border membrane where it facilitates the uptake of dietary cholesterol from either bile salt micelles or phospholipid vesicles. This receptor can also function as a port for several additional classes of lipids, including cholesteryl esters, triacylglycerols, and phospholipids. It is the first receptor demonstrated to be involved in the absorption of dietary lipids in the intestine. In liver and steroidogenic tissues, the physiological ligand of this receptor is high-density lipoprotein. We show that binding of high-density lipoprotein and apolipoprotein A-I to the brush border membrane-resident receptor inhibits uptake of cholesterol (sterol) into the brush border membrane from lipid donor particles. This finding lends further support to the conclusion that scavenger receptor BI catalyzes intestinal cholesterol uptake. Our findings suggest new therapeutic approaches for limiting the absorption of dietary cholesterol and reducing hypercholesterolemia and the risk of atherosclerosis.

A systematic nomenclature for allergens originated in the early 1980s, when few protein allergens had been described. A group of scientists led by Dr. David G. Marsh developed a nomenclature based on the Linnaean taxonomy, and further established the World Health Organization/International Union of Immunological Societies (WHO/IUIS) Allergen Nomenclature Sub-Committee in 1986. Its stated aim was to standardize the names given to the antigens (allergens) that caused IgE-mediated allergies in humans. The Sub-Committee first published a revised list of allergen names in 1986, which continued to grow with rare publications until 1994. Between 1994 and 2007 the database was a text table online, then converted to a more readily updated website. The allergen list became the Allergen Nomenclature database (www.allergen.org), which currently includes approximately 880 proteins from a wide variety of sources. The Sub-Committee includes experts on clinical and molecular allergology. They review submissions of allergen candidates, using evidence-based criteria developed by the Sub-Committee. The review process assesses the biochemical analysis and the proof of allergenicity submitted, and aims to assign allergen names prior to publication. The Sub-Committee maintains and revises the database, and addresses continuous challenges as new "omics" technologies provide increasing data about potential new allergens. Most journals publishing information on new allergens require an official allergen name, which involves submission of confidential data to the WHO/IUIS Allergen Nomenclature Sub-Committee, sufficient to demonstrate binding of IgE from allergic subjects to the purified protein.

The seventh “Future of the Allergists and Specific Immunotherapy (FASIT)” workshop held in 2019 provided a platform for global experts from academia, allergy clinics, regulatory authorities and industry to review current developments in the field of allergen immunotherapy (AIT). Key domains of the meeting included the following: (a) Biomarkers for AIT and allergic asthma; (b) visions for the future of AIT; (c) progress and data for AIT in asthma and the updates of GINA and EAACI Asthma Guidelines (separated for house dust mite SCIT, SLIT tablets and SLIT drops; patient populations) including a review of clinically relevant endpoints in AIT studies in asthma; (d) regulatory prerequisites such as the “Therapy Allergen Ordinance” in Germany; (e) optimization of trial design in AIT clinical research; (f) challenges planning and conducting phase III (field) studies and the future role of Allergen Exposure Chambers (AEC) in AIT product development from the regulatory point of view. We report a summary of panel discussions of all six domains and highlight unmet needs and possible solutions for the future.

Crystal structures of the wild type human medium-chain acyl-CoA dehydrogenase (MCADH) and a double mutant in which its active center base-arrangement has been altered to that of long chain acyl-CoA dehydrogenase (LCADH), Glu376Gly/Thr255Glu, have been determined by X-ray crystallography at 2.75 and 2.4 Å resolution, respectively. The catalytic base responsible for the R-proton abstraction from the thioester substrate is Glu376 in MCADH, while that in LCADH is Glu255 (MCADH numbering), located over 100 residues away in its primary amino acid sequence. The structures of the mutant complexed with C8-, C12, and C14-CoA have also been determined. The human enzyme structure is essentially the same as that of the pig enzyme. The structure of the mutant is unchanged upon ligand binding except for the conformations of a few side chains in the active site cavity. The substrate with chain length longer than C12 binds to the enzyme in multiple conformations at its ω-end. Glu255 has two conformations, "active" and "resting" forms, with the latter apparently stabilized by forming a hydrogen bond with Glu99. Both the direction in which Glu255 approaches the C R atom of the substrate and the distance between the Glu255 carboxylate and the C R atom are different from those of Glu376; these factors are responsible for the intrinsic differences in the kinetic properties as well as the substrate specificity. Solvent accessible space at the "midsection" of the active site cavity, where the C R -C bond of the thioester substrate and the isoalloxazine ring of the FAD are located, is larger in the mutant than in the wild type enzyme, implying greater O 2 accessibility in the mutant which might account for the higher oxygen reactivity.Acyl-CoA dehydrogenases are a family of flavoenzymes that catalyze the R, -dehydrogenation of acyl-CoA thioesters to the corresponding trans-enoyl-CoA with transfer of reducing equivalents to electron transfer flavoprotein (Beinert, 1963). In mammalian mitochondria, four straight-chain specific acyl-CoA dehydrogenases [short (SCADH)-, medium (MCADH)-, long (LCADH)-, and very long chain (VLCAD) acyl-CoA dehydrogenase] involved in fatty acid catabolism (Beinert, 1963;Aoyama et al., 1994) and three branched-chain specific acyl-CoA dehydrogenases (isovaleryl-, 2-methylbutyryl-, and glutaryl-CoA-DH) in amino acid metabolism have been described (Tanaka & Indo, 1992;Lenich & Goodman, 1986). Among them, MCADH is the most studied: the three dimensional structure of pig MCADH has been determined with and without various substrates and inhibitors (Kim et al., 1993 and its catalytic residue has been identified (Powell & Thorpe, 1988) and confirmed by site-specific mutagenesis (Bross, et al, 1990) and by the three dimensional structures of enzyme-substrate complex (Kim et al., 1993). All seven acyl-CoA dehydrogenases have been cloned, sequenced, and over-expressed in bacterial systems. Of the 27 known amino acid sequences of acylCoA dehydrogenases from both mammalian and bacterial sources available, the catal...

The IUIS Allergen Nomenclature Sub-Committee, under the auspices of the World Health Organization and the International Union of Immunological Societies, maintains the systematic nomenclature of allergenic proteins and publishes a database of approved allergen names on its Web site, www.allergen.org. In this paper, we summarize updates of allergen names approved at the meetings of the committee in 2011 through 2013. These changes reflect recent progress in identification, cloning, and sequencing of allergens. The goals of this update were to increase consistency in the classification of allergens, isoallergens, and variants and in the incorporation of the evolutionary classification of proteins into allergen nomenclature, while keeping changes of established names to a minimum in the interest of continuity. Allergens for which names have been updated include respiratory allergens from birch and ragweed pollen, midge larvae, and horse dander; food allergens from peanut, cow's milk, and tomato; and cereal grain allergens. The IUIS Allergen Nomenclature Sub-Committee encourages researchers to use these updated allergen names in future publications.The official nomenclature of allergenic proteins is based on the Linnaean binominal nomenclature identifying genus and species of all organisms and was first published in 1986 (1) and revised in 1994 (2-6). The allergen nomenclature is maintained by the IUIS Allergen Nomenclature Sub-Committee under the auspices of the World Health Organization (WHO) and the International Union of Immunological Societies (IUIS). The committee maintains the database of approved allergen names (www.allergen.org), which has developed from a plain text list to a fully functional, searchable database. In order to maintain a consistent allergen nomenclature that complies with the guidelines established by the subcommittee, researchers are required to submit newly described allergens to the Allergen Nomenclature Sub-Committee before submitting their manuscript to a journal for consideration for publication. Submissions are kept confidential by the subcommittee, and no specific information other than the name of the new allergen will be disclosed on the Web site before publication. The submission form is available at www.allergen.org.Allergen names are composed of an abbreviation of the scientific name of its source (genus: 3-4 letters; species: 1-2 letters) and an Arabic numeral, for example Der p 1 for the first allergen to be described from the house dust mite Dermatophagoides pteronyssinus. Originally, new allergens were assigned consecutive numbers. During the past decades, the increase in sequence data together with advances in bioinformatics made it possible to classify allergens into protein families whose members are evolutionary related, have Allergy 69 (2014) 413-419

The catalytically essential glutamate residue that initiates catalysis by abstracting the substrate R-hydrogen as H + is located at position 376 (mature MCADH numbering) on loop JK in medium chain acyl-CoA dehydrogenase (MCADH). In long chain acyl-CoA dehydrogenase (LCADH) and isovalerylCoA dehydrogenase (IVDH), the corresponding Glu carrying out the same function is placed at position 255 on the adjacent helix G. These glutamates thus act on substrate approaching from two opposite regions at the active center. We have implemented the topology of LCADH in MCADH by carrying out the two mutations Glu376Gly and Thr255Glu. The resulting chimeric enzyme, "medium-/long" chain acyl-CoA dehydrogenase (MLCADH) has ∼20% of the activity of MCADH and ∼25% that of LCADH with its best substrates octanoyl-CoA and dodecanoyl-CoA, respectively. MLCADH exhibits an enhanced rate of reoxidation with oxygen, however, with a much narrower substrate chain length specificity that peaks with dodecanoyl-CoA. This is the same maximum as that of LCADH and is thus significantly shifted from that of native MCADH (hexanoyl/octanoyl-CoA). The putative, common ancestor of LCADH and IVDH has two Glu residues, one each at positions 255 and 376. The corresponding MCADH mutant, Thr255Glu (glu/glu-MCADH), is as active as MCADH with octanoyl-CoA; its activity/chain length profile is, however, much narrower. The topology of the Glu as H + abstracting base seems an important factor in determining chain length specificity and reactivity in acyl-CoA dehydrogenases. The mechanisms underlying these effects are discussed in view of the three-dimensional structure of MLCADH, which is presented in the accompanying paper [Lee et al. (1996) Biochemistry 35, 12412-12420].Acyl-CoA dehydrogenases are a class of flavoproteins that catalyze the desaturation of acyl-CoA substrates. Four known members are involved in mammalian mitochondrial -oxidation of fatty acids (short-, medium-, long-, and very long chain acyl-CoA dehydrogenases), and three (isovaleryl-, isobutyryl-and glutaryl-CoA dehydrogenases) are involved in the degradation of amino acids. In addition microsomal or peroxisomal acyl-CoA oxidases and a variety of related enzymes of bacterial or plant origin can be viewed as sharing the capacity to catalyze the seemingly identical chemical process, the substrate dehydrogenation at the positions R, .

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