ABC Transporters in Microorganisms This book represents an interdisciplinary review of the role of ABC transporters in microorganisms, combining data from structural biology, biochemistry, clinical research and pharmacology. ABC (ATP binding cassette) transporters are ubiquitous membrane protein complexes and constitute a large superfamily of primary active transport systems. They couple the energy from ATP hydrolysis to the translocation of a large variety of substrate across biological membranes. The dysfunction of several ABC transporters is involved in human pathologies such as cystic fibrosis, and adrenoleukodystrophy, or confers resistance to antibiotics and chemotherapeutic agents to tumour cells. In this context, it is highly desirable to study the structure and the molecular dynamics of ABC transport systems to get insight into the complex mechanisms of ATP binding and hydrolysis and the subsequent substrate translocation. That turns them into a fundamental field of research. “ABC transporters in Microorganisms: Research, Innovation and Value as Targets against Drug Resistance” is an excellent summing up of data from structural, biochemical as well as clinical investigations of ABC transporters. The main focus is drawn on multidrug resistance-linked members of this protein superfamily. In the first chapter the state-of-the-art of structural and functional investigations is presented. The authors describe organization and topology of ABC transporters and the putative signaling pathway. The transport and the connected ATP hydolysis are discussed on the basis of data from 3D structures of the isolated nucleotide binding sites as well as the full transporters and biochemical experiments. The following chapters depict the role of ABC transporters in multidrug resistance in bacteria and cancer cells. Several questions regarding evolution and function of multidrug resistance and its importance for survival of bacteria are discussed. In chapter six ABC transporters of Plasmodium falciparum proposed to be involved in antimalarial drug resistance, which creates a severe problem in prevention and treatment of malaria, are presented. The authors emphasize the recent developments on inhibitors and modulators of Chloroquine, quinine and mefloquine resistance. In chapter 7 the identified ABC transporters from the Trypanosomatidae family are summarized. They are involved in vesicular trafficking, phospholipids movement and drug resistance. As a conclusion two therapy approaches to overcome multidrug resistance mediated by ABC transporters are discussed. The closing chapters deal with the development of ABC transporter blockers and RNA interference-mediated reversal of multidrug resistance in microorganisms. This book is a comprehensive review with a general outline given in each chapter that is essential and useful not only for readers interested in the fascinating ABC transporter family.

This book represents an interdisciplinary review of the role of ABC transporters in microorganisms, combining data from structural biology, biochemistry, clinical research and pharmacology.

ABC (ATP binding cassette) transporters are ubiquitous membrane protein complexes and constitute a large superfamily of primary active transport systems. They couple the energy from ATP hydrolysis to the translocation of a large variety of substrate across biological membranes. The dysfunction of several ABC transporters is involved in human pathologies such as cystic fibrosis, and adrenoleukodystrophy, or confers resistance to antibiotics and chemotherapeutic agents to tumour cells. In this context, it is highly desirable to study the structure and the molecular dynamics of ABC transport systems to get insight into the complex mechanisms of ATP binding and hydrolysis and the subsequent substrate translocation. That turns them into a fundamental field of research.

“ABC transporters in Microorganisms: Research, Innovation and Value as Targets against Drug Resistance” is an excellent summing up of data from structural, biochemical as well as clinical investigations of ABC transporters. The main focus is drawn on multidrug resistance-linked members of this protein superfamily.

In the first chapter the state-of-the-art of structural and functional investigations is presented. The authors describe organization and topology of ABC transporters and the putative signaling pathway. The transport and the connected ATP hydolysis are discussed on the basis of data from 3D structures of the isolated nucleotide binding sites as well as the full transporters and biochemical experiments.

The following chapters depict the role of ABC transporters in multidrug resistance in bacteria and cancer cells. Several questions regarding evolution and function of multidrug resistance and its importance for survival of bacteria are discussed.

In chapter six ABC transporters of Plasmodium falciparum proposed to be involved in antimalarial drug resistance, which creates a severe problem in prevention and treatment of malaria, are presented. The authors emphasize the recent developments on inhibitors and modulators of Chloroquine, quinine and mefloquine resistance.

In chapter 7 the identified ABC transporters from the Trypanosomatidae family are summarized. They are involved in vesicular trafficking, phospholipids movement and drug resistance.

As a conclusion two therapy approaches to overcome multidrug resistance mediated by ABC transporters are discussed. The closing chapters deal with the development of ABC transporter blockers and RNA interference-mediated reversal of multidrug resistance in microorganisms.

This book is a comprehensive review with a general outline given in each chapter that is essential and useful not only for readers interested in the fascinating ABC transporter family.

geschrieben am 01.10.2009 | 409 Wörter | 2491 Zeichen