دورية أكاديمية
New light on multidrug binding by an ATP-binding-cassette transporter.
| العنوان: | New light on multidrug binding by an ATP-binding-cassette transporter. |
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| المؤلفون: | Shilling RA; Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, UK, CB2 1PD., Venter H, Velamakanni S, Bapna A, Woebking B, Shahi S, van Veen HW |
| المصدر: | Trends in pharmacological sciences [Trends Pharmacol Sci] 2006 Apr; Vol. 27 (4), pp. 195-203. Date of Electronic Publication: 2006 Mar 20. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Published By Elsevier In Association With The International Union Of Pharmacology Country of Publication: England NLM ID: 7906158 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0165-6147 (Print) Linking ISSN: 01656147 NLM ISO Abbreviation: Trends Pharmacol Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Barking : Published By Elsevier In Association With The International Union Of Pharmacology Original Publication: Amsterdam, Published by Elsevier in association with the International Union of Pharmacology. |
| مواضيع طبية MeSH: | ATP Binding Cassette Transporter, Subfamily B, Member 1/*chemistry , ATP Binding Cassette Transporter, Subfamily B, Member 1/*metabolism , ATP-Binding Cassette Transporters/*chemistry , ATP-Binding Cassette Transporters/*metabolism, ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics ; ATP-Binding Cassette Transporters/genetics ; Amino Acid Sequence ; Animals ; Antineoplastic Agents/metabolism ; Binding Sites/genetics ; Biological Transport ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Structure, Tertiary |
| مستخلص: | ATP-binding-cassette (ABC) multidrug transporters confer multidrug resistance to pathogenic microorganisms and human tumour cells by mediating the extrusion of structurally unrelated chemotherapeutic drugs from the cell. The molecular basis by which ABC multidrug transporters bind and transport drugs is far from clear. Genetic analyses during the past 14 years reveal that the replacement of many individual amino acids in mammalian multidrug resistance P-glycoproteins can affect cellular resistance to drugs, but these studies have failed to identify specific regions in the primary amino acid sequence that are part of a defined drug-binding pocket. The recent publication of an X-ray crystallographic structure of the bacterial P-glycoprotein homologue MsbA and an MsbA-based homology model of human P-glycoprotein creates an opportunity to compare the original mutagenesis data with the three-dimensional structures of transporters. Our comparisons reveal that mutations that alter specificity are present in three-dimensional 'hotspot' regions in the membrane domains of P-glycoprotein. |
| Number of References: | 75 |
| معلومات مُعتمدة: | G0401165 United Kingdom MRC_ Medical Research Council |
| المشرفين على المادة: | 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1) 0 (ATP-Binding Cassette Transporters) 0 (Antineoplastic Agents) |
| تواريخ الأحداث: | Date Created: 20060321 Date Completed: 20060615 Latest Revision: 20220129 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.tips.2006.02.008 |
| PMID: | 16545467 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 0165-6147 |
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| DOI: | 10.1016/j.tips.2006.02.008 |