Transporters catalyze entry and exit of molecules into and out of cells and organelles. They achieve cellular homeostasis, are responsible for multidrug resistance in pathogens and tumors, and, when defective, cause dozens of important human genetic diseases. Our laboratory maintains, updates and improves the Transporter Classification Database, TCDB, which houses the Transporter Classification (TC) system, adopted officially by the International Union of Biochemistry and Molecular Biology (IUBMB). TCDB is the internationally acclaimed, carefully annotated, universal standard for classifying and providing information about transporters and transport-related proteins in all major domains of life. It presents sequence, biochemical, physiological, pathological, structural and evolutionary data about these proteins and the transport systems they comprise. It uses a successful system of classification based on transporter class, subclass, family, subfamily, individual transport system and constituent proteins. It also includes a superfamily hyperlink. In this competitive renewal of GM0077402, we propose to continue to expand, update, and semi-automate TCDB.
Our specific aims are to (1) upgrade TCDB by characterizing and categorizing protein domains and their topologies, motifs, repeat units, functional interactions, alternative splicing and post-translational modifications, (2) expand TCDB by implementing novel pipelines for data entry that will increase the coverage of transport diversity in TCDB while describing more effectively the complexity of multicomponent transport systems, (3) enter into TCDB transporter modulators such as activators, inhibitors, drugs and xenobiotics as well as internal and external conditions that influence transporter activities, while generating an ontology to describe the effects of chemical modulators that will complement our substrate ontology, (4) incorporate into TCDB synthetic pores/channels (TC subclass 1.D), and carriers (TC subclass 2.B), (5) introduce into TCDB connections between transport and metabolism and (6) expand our plans for long-term TCDB sustainability.
TCDB is the only IUBMB-approved database providing the worldwide scientific community with systematic information about proteins that catalyze transmembrane transport. Transport proteins play critical roles in health-related issues such as personalized medicine, cancer, drug development, bacterial pathogenesis and antimicrobial resistance. Funding of this proposal will allow us to provide research results, as well as high-quality data and software for the identification of transporter proteins useful to scientists whose investigations focus on health issues.
|Babu, Mohan; Bundalovic-Torma, Cedoljub; Calmettes, Charles et al. (2018) Global landscape of cell envelope protein complexes in Escherichia coli. Nat Biotechnol 36:103-112|
|Rodionova, Irina A; Goodacre, Norman; Babu, Mohan et al. (2018) The Nitrogen Regulatory PII Protein (GlnB) and N-Acetylglucosamine 6-Phosphate Epimerase (NanE) Allosterically Activate Glucosamine 6-Phosphate Deaminase (NagB) in Escherichia coli. J Bacteriol 200:|
|Moreno-Hagelsieb, Gabriel; Vitug, Bennett; Medrano-Soto, Arturo et al. (2017) The Membrane Attack Complex/Perforin Superfamily. J Mol Microbiol Biotechnol 27:252-267|
|Lee, Justin; Ghosh, Shounak; Saier Jr, Milton H (2017) Comparative genomic analyses of transport proteins encoded within the red algae Chondrus crispus, Galdieria sulphuraria, and Cyanidioschyzon merolae11. J Phycol 53:503-521|
|Zhang, Zhongge; Kukita, Chika; Humayun, M Zafri et al. (2017) Environment-directed activation of the Escherichia coliflhDC operon by transposons. Microbiology 163:554-569|
|Saier Jr, Milton H; Kukita, Chika; Zhang, Zhongge (2017) Transposon-mediated directed mutation in bacteria and eukaryotes. Front Biosci (Landmark Ed) 22:1458-1468|
|Heidari Tajabadi, Fereshteh; Medrano-Soto, Arturo; Ahmadzadeh, Masoud et al. (2017) Comparative Analyses of Transport Proteins Encoded within the Genomes of Bdellovibrio bacteriovorus HD100 and Bdellovibrio exovorus JSS. J Mol Microbiol Biotechnol 27:332-349|
|Do, Jimmy; Zafar, Hassan; Saier Jr, Milton H (2017) Comparative genomics of transport proteins in probiotic and pathogenic Escherichia coli and Salmonella enterica strains. Microb Pathog 107:106-115|
|Humayun, M Zafri; Zhang, Zhongge; Butcher, Anna M et al. (2017) Hopping into a hot seat: Role of DNA structural features on IS5-mediated gene activation and inactivation under stress. PLoS One 12:e0180156|
|Saier Jr, Milton H; Trevors, J T (2017) Science, Innovation and the Future of Humanity. J Mol Microbiol Biotechnol 27:128-132|
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