ABC transporter: Difference between revisions
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'''Function''' | |||
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ABC Transporters has two main functionality acting either as exporters or importers. '''ABC Exporters''' release bound drugs to the extracellular environment, while '''ABC Importers''' accept substrate molecules from their relevant substrate-binding proteins<ref name="biochembook"/>. | ABC Transporters has two main functionality acting either as exporters or importers. '''ABC ''Exporters''''' release bound drugs to the extracellular environment, while '''ABC ''Importers''''' accept substrate molecules from their relevant substrate-binding proteins<ref name="biochembook"/>. For instance the Vitamin B12 transporter BtuCD (PDB [[1l7v]]) is a binding protein-dependent ABC transporter system that uses the power of ATP hydrolysis to pump vitamin B12 into the cytoplasm of E. coli<ref name="BtuCD-Ecoli"/>. | ||
'''ABC Exporters''' Use ATP to drive import and export functions providing multidrug resistance. In eukaryoles, for instance, ABC Transporters are problematic because they export therapeutic drugs such as those used in chemotherapy regimens, which must be changed frequently to avoid the rejection of the drugs<ref name="biochembook"/>. | '''ABC Exporters''' Use ATP to drive import and export functions providing multidrug resistance. In eukaryoles, for instance, ABC Transporters are problematic because they export therapeutic drugs such as those used in chemotherapy regimens, which must be changed frequently to avoid the rejection of the drugs<ref name="biochembook"/>. | ||
To achieve export, ABC transporters require a minimum of four domains. Two transmembrane domains (TMDs) form the ligand binding sites and provide specificity, and two NBDs bind and hydrolyze ATP to drive the trans-location of the bound ligand. The NBDs, but not the TMDs, are homologous throughout the family and have several characteristic motifs including the Walker A and B motifs common to many nucleotide binding proteins and others like the ABC signature, stacking aromatic D, H, and Q loops, which are unique to the family<ref name="FourDomainsABCT"/>. | To achieve export, ABC transporters require a minimum of four domains. Two transmembrane domains (TMDs) form the ligand binding sites and provide specificity, and two NBDs bind and hydrolyze ATP to drive the trans-location of the bound ligand. The NBDs, but not the TMDs, are homologous throughout the family and have several characteristic motifs including the Walker A and B motifs common to many nucleotide binding proteins and others like the ABC signature, stacking aromatic D, H, and Q loops, which are unique to the family<ref name="FourDomainsABCT"/>. | ||
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<ref name="Kidney">[http://jpet.aspetjournals.org/content/328/1/3 Huls et al. The Role of ATP Binding Cassette Transporters in Tissue Defense and Organ Regeneration. Journal of Pharmacology and Experimental Therapeutics, 2008; 328 (1)]</ref> | <ref name="Kidney">[http://jpet.aspetjournals.org/content/328/1/3 Huls et al. The Role of ATP Binding Cassette Transporters in Tissue Defense and Organ Regeneration. Journal of Pharmacology and Experimental Therapeutics, 2008; 328 (1)]</ref> | ||
<ref name="BtuCD-Ecoli">[http://thesis.library.caltech.edu/9/ Borths EL. Structural and biochemical characterization of the vitamin B12 ABC transporter, BtuCD-F. Dissertation (Ph.D.), California Institute of Technology. 2005]</ref> | |||
<ref name="EColi">[http://cel.isiknowledge.com/InboundService.do?product=CEL&action=retrieve&SrcApp=Highwire&UT=000073122300002&SID=4Bba9dOeogjJfpPPHmP&Init=Yes&SrcAuth=Highwire&mode=FullRecord&customersID=Highwire Linton KJ, Higgins CF. The Escherichia coli ATP-binding cassette (ABC) proteins. Mol Microbiol 28: 5–13, 1998]</ref> | <ref name="EColi">[http://cel.isiknowledge.com/InboundService.do?product=CEL&action=retrieve&SrcApp=Highwire&UT=000073122300002&SID=4Bba9dOeogjJfpPPHmP&Init=Yes&SrcAuth=Highwire&mode=FullRecord&customersID=Highwire Linton KJ, Higgins CF. The Escherichia coli ATP-binding cassette (ABC) proteins. Mol Microbiol 28: 5–13, 1998]</ref> | ||
<ref name="biochembook">[http://physiologyonline.physiology.org/cgi/content/full/22/2/122 Linton KJ. Structure and Function of ABC Transporters. Physiology 22: 122-130, 2007; doi:10.1152/physiol.00046.2006]</ref> | <ref name="biochembook">[http://physiologyonline.physiology.org/cgi/content/full/22/2/122 Linton KJ. Structure and Function of ABC Transporters. Physiology 22: 122-130, 2007; doi:10.1152/physiol.00046.2006]</ref> | ||
<ref name="FourDomainsABCT">[http://books.google.com/books?id=iGPsen3fSOIC&printsec=frontcover&dq=Biochemistry++By+Reginald+Garrett,+Charles+M.+Grisham&hl=en&ei=MOv3TP3eHsSAlAer0K2OAg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CDMQ6AEwAA#v=onepage&q&f=false Garrett R, Grisham CM. Biochemistry. 2008. 1059 pages]</ref> | <ref name="FourDomainsABCT">[http://books.google.com/books?id=iGPsen3fSOIC&printsec=frontcover&dq=Biochemistry++By+Reginald+Garrett,+Charles+M.+Grisham&hl=en&ei=MOv3TP3eHsSAlAer0K2OAg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CDMQ6AEwAA#v=onepage&q&f=false Garrett R, Grisham CM. Biochemistry. 2008. 1059 pages]</ref> | ||
}} | }} | ||
Revision as of 01:18, 3 December 2010
ATP Binding Cassette (ABC) Transporters are ATP-dependent membrane proteins critical for most aspects of cell physiology, including the uptake of nutrients (importers) and elimination of waste products and energy generation (exporters) which are predominantly expressed in excretory organs, such as the liver, intestine, blood-brain barrier, blood-testes barrier, placenta, and kidney[1][2]. There are many ABC Transporters in organisms, for instance, there are 28 in Saccharomyces,58 in Caenorhabditis, 51 in Drosophila,129 in Arabadopsis,and the 69 ABC transporters in E. coli account for almost 5% of its genomic coding capacity[3].
Function
ABC Transporters has two main functionality acting either as exporters or importers. ABC Exporters release bound drugs to the extracellular environment, while ABC Importers accept substrate molecules from their relevant substrate-binding proteins[4]. For instance the Vitamin B12 transporter BtuCD (PDB 1l7v) is a binding protein-dependent ABC transporter system that uses the power of ATP hydrolysis to pump vitamin B12 into the cytoplasm of E. coli[5].
ABC Exporters Use ATP to drive import and export functions providing multidrug resistance. In eukaryoles, for instance, ABC Transporters are problematic because they export therapeutic drugs such as those used in chemotherapy regimens, which must be changed frequently to avoid the rejection of the drugs[4].
To achieve export, ABC transporters require a minimum of four domains. Two transmembrane domains (TMDs) form the ligand binding sites and provide specificity, and two NBDs bind and hydrolyze ATP to drive the trans-location of the bound ligand. The NBDs, but not the TMDs, are homologous throughout the family and have several characteristic motifs including the Walker A and B motifs common to many nucleotide binding proteins and others like the ABC signature, stacking aromatic D, H, and Q loops, which are unique to the family[2].
- References
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