Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

UniProt release 2019_03

Published April 10, 2019

Headline

A drug arsenal from lupins

Digging into traditional medicines to find new drugs is a proven and fruitful strategy. Think of forskolin, a very effective activator of adenylate cyclase, used daily in numerous laboratories. This agent is produced by the Ayurvedic herb Plectranthus barbatus, which used to be recommended, among others, to treat cardiovascular disorders. Or the anticancer drug paclitaxel (taxol), isolated from Taxus brevifolia, the Pacific yew. Or artemisinin, the most efficient treatment against malaria, which derives from Artemisia annua, also called sweet wormwood, a herb employed in Chinese traditional medicine. Plant metabolites and direct derivatives thereof constitute more than a third of currently approved pharmaceuticals. Lupin seeds also belong to the traditional pharmacopoeia on all continents where it has been cultivated. The great Persian physician Avicenna recommended lupin seed flour, mixed with fenugreek and zedoary, to treat diabetes, as he noticed that this mixture considerably decreased sugar excretion in patients. A thousand years after his observation, the lupin protein mediating this effect, gamma-conglutin, has been identified.

In the lupin seed, most conglutins are storage proteins, which are hydrolyzed during germination and nourish the early stages of seedling growth. By contrast, gamma-conglutin is resistant to proteolysis. In this context, its physiological role in the seed is puzzling, but we have a little more insight into its effect on mammalian cells and organisms. Magni et al. reported that hyperglycemic rats experienced a substantial normalization of blood glucose levels after oral administration of white lupin (Lupinus albus) gamma-conglutin. The decrease in sugar blood level was comparable to that obtained with metformin, a well-established medication for the treatment of type 2 diabetes. This observation was later confirmed and extended to small groups of human volunteers.

After ingestion, gamma-conglutin is not digested in the gastrointestinal tract and the intact protein may be translocated across the intestinal barrier through transcytosis. Once in the blood, it may act at several levels. It seems to bind insulin and may potentiate its activity. When myocytes are incubated with gamma-conglutin, they activate signaling pathways similar to those of insulin, including the activation of the insulin receptor substrate 1 (IRS1), AKT1, and EIF4EBP1/PHAS1. Gamma-conglutin peptides produced in vitro can also inhibit dipeptidyl peptidase-4 (DPP4), an enzyme which degrades incretins, a group of metabolic hormones that stimulate a decrease in blood glucose levels. Gamma-conglutin also enhances the cell surface expression of glucose transporters, including SLC2A4 (GLUT4), and inhibits gluconeogenesis in hepatocytes.

More investigations are needed before gamma-conglutin becomes a drug for type 2 diabetes, but in view of the dynamics of the diabetes epidemic, it seems that nature may be giving us a hand in new drug development.

It’s time now for you to enjoy a lupin bean snack and consult our newly annotated UniProtKB/Swiss-Prot lupin gamma-conglutin entries.

UniProt website news

Search for small molecules via InChiKey

We have recently enhanced enzyme annotation in UniProtKB using Rhea, a comprehensive expert-curated knowledgebase of biochemical reactions that uses the ChEBI (Chemical Entities of Biological Interest) ontology to describe reaction participants, their chemical structures, and chemical transformations. We also use ChEBI to annotate enzyme cofactors in UniProtKB.

You can now search UniProtKB for small molecule reaction participants and cofactors using the InChIKey, a standard hashed representation of the IUPAC International Chemical Identifier (InChI) that provides a unique and compact representation of chemical structure data. The UniProt website supports flexible chemical structure searches with the complete InChIKey, as well as with the connectivity and stereochemistry layers, or the connectivity layer alone. You can search our “Catalytic activity” or “Cofactor” annotations, or both combined, by using the new “Small molecule” advanced search field:

This new InChIKey-based search will help unlock the power of chemical structure data in UniProtKB, particularly when combined with our existing search tools and options for biological data. It complements the chemical ontology search, which allows users to search UniProtKB for chemical classes of biological interest like lipids, amino acids, sugars and specializations thereof, using identifiers from the ChEBI ontology of small molecules.

See How can I search UniProt for chemical or reaction data?

UniProtKB news

Changes to the controlled vocabulary of human diseases

New diseases:

Modified disease:

Changes to the controlled vocabulary for PTMs

New term for the feature key ‘Modified residue’ (‘MOD_RES’ in the flat file):

  • (Z)-2,3-didehydroaspartate
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again