Crystal Structures of the MJ1267 ATP Binding Cassette Reveal an Induced-Fit Effect at the ATPase Active Site of an ABC Transporter

Karpowich, Nathan K.; Martsinkevich, Oksana; Millen, Linda; Yuan, Yu; Dai, Peter L.; MacVey, Karen; Thomas, Philip; Hunt, J.F.

doi:10.1016/s0969-2126(01)00617-7

Cited by 284 publications

(346 citation statements)

References 60 publications

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“…However, an extensive structural analysis was performed to address dimer formation. Special attention was placed on the solvent-accessible surface area (ASA), buried in the dimer interface of HisP, MalK, Rad50cd and the potential dimers of MJ0796 and of MJ1267 (Karpowich et al 2001a). The analysis revealed that, with the exception of Rad50cd and MalK, all the ASAs were equivalent to those commonly found for crystal packing contacts, rather than for oligomeric complexes (Janin 1997).…”

Section: Dimeric Arrangement -Problems and Solutionsmentioning

confidence: 99%

“…This suggests that, upon ATP binding, these regions might be stabilized and possibly also take on another position in the ATP bound state. Furthermore, Karpowich et al (2001b) extensively analyzed the B-factors in the different nucleotide bound forms of MJ1267. Here the nucleotide-free structure shows higher overall B-factors compared to the Mg*ADP bound form.…”

Section: The Intrinsic Flexibility Of the Apo Nbd Formsmentioning

confidence: 99%

“…Here the nucleotide-free structure shows higher overall B-factors compared to the Mg*ADP bound form. Additionally, however, the structure also has especially elevated regions corresponding to the nucleotide binding regions, Walker A, D-loop and H-loop (Karpowich et al 2001b). This clearly implies that upon nucleotide binding the protein conformation is fixed, especially in the area generating the nucleotide-binding site.…”

Section: The Intrinsic Flexibility Of the Apo Nbd Formsmentioning

confidence: 99%

“…The analysis of the MJ1267 structures in the nucleotide free and Mg*ADP bound forms, in comparison with the ATP bound form of HisP resulted in the postulation of an induced fit mechanism (Karpowich et al 2001b). This described the structural changes at the binding site as the consequence of ATP binding.…”

Section: The Induced Fit Effect and The Rotational Movement Of The Hementioning

confidence: 99%

“…The binding of ATP to the monomer results in an induced fit effect (Karpowich et al 2001a (Smith and Rayment 1996). The radioactively labeled nucleotides are either (Fig.…”

Section: Structural Aspectsmentioning

confidence: 99%

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The motor domains of ABC-transporters

Oswald

Holland

Schmitt

2006

Naunyn Schmied Arch Pharmacol

133

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The transport of substrates across a cellular membrane is a vitally important biological function essential for cell survival. ATP-binding cassette (ABC) transporters constitute one of the largest subfamilies of membrane proteins, accomplishing this task. Mutations in genes encoding for ABC transporters cause different diseases, for example, Adrenoleukodystrophy, Stargardt disease or Cystic Fibrosis. Furthermore, some ABC transporters are responsible for multidrug resistance, presenting a major obstacle in modern cancer chemotherapy. In order to translocate the enormous variety of substrates, ranging from ions, nutrients, small peptides to large toxins, different ABC-transporters utilize the energy gained from ATP binding and hydrolysis. The ATP binding cassette, also called the motor domain of ABC transporters, is highly conserved among all ABC transporters. The ability to purify this domain rather easily presents a perfect possibility to investigate the mechanism of ATP hydrolysis, thus providing us with a detailed picture of this process. Recently, many crystal structures of the ATP-binding domain and the full-length structures of two ABC transporters have been solved. Combining these structural data, we have now the opportunity to analyze the hydrolysis event on a molecular level. This review provides an overview of the structural investigations of the ATPbinding domains, highlighting molecular changes upon ATP binding and hydrolysis.

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Section: Dimeric Arrangement -Problems and Solutionsmentioning

confidence: 99%

Section: The Intrinsic Flexibility Of the Apo Nbd Formsmentioning

confidence: 99%

Section: The Intrinsic Flexibility Of the Apo Nbd Formsmentioning

confidence: 99%

Section: The Induced Fit Effect and The Rotational Movement Of The Hementioning

confidence: 99%

“…The binding of ATP to the monomer results in an induced fit effect (Karpowich et al 2001a (Smith and Rayment 1996). The radioactively labeled nucleotides are either (Fig.…”

Section: Structural Aspectsmentioning

confidence: 99%

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The motor domains of ABC-transporters

Oswald

Holland

Schmitt

2006

Naunyn Schmied Arch Pharmacol

133

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ABC‐F translation factors: from antibiotic resistance to immune response

et al. 2020

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Energy-dependent Translational Throttle A (EttA) from E. coli is a paradigmatic ABC-F protein that controls the first step in polypeptide elongation on the ribosome according to the cellular energy status. Biochemical and structural studies have established that ABC-F proteins generally function as translation factors that modulate the conformation of the peptidyl transferase center upon binding to the ribosomal tRNA exit site. These factors, present in both prokaryotes and eukaryotes but not in archaea, use related molecular mechanisms to modulate protein synthesis for heterogenous purposes, ranging from antibiotic resistance and rescue of stalled ribosomes to modulation of the mammalian immune response. Here we review the canonical studies characterizing the phylogeny, regulation, ribosome interactions, and mechanisms of action of the bacterial ABC-F proteins, and discuss the implications of these studies for the molecular function of eukaryotic ABC-F proteins, including the three human family members.

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The role of the degenerate nucleotide binding site in type I ABC exporters

2020

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ATP-binding cassette (ABC) transporters are fascinating molecular machines that are capable of transporting a large variety of chemically diverse compounds. The energy required for translocation is derived from binding and hydrolysis of ATP. All ABC transporters share a basic architecture and are composed of two transmembrane domains and two nucleotide binding domains (NBDs). The latter harbor all conserved sequence motifs that hallmark the ABC transporter superfamily. The NBDs form the nucleotide binding sites (NBSs) in their interface. Transporters with two active NBSs are called canonical transporters, while ABC exporters from eukaryotic organisms, including humans, frequently have a degenerate NBS1 containing noncanonical residues that strongly impair ATP hydrolysis. Here, we summarize current knowledge on degenerate ABC transporters. By integrating structural information with biophysical and biochemical evidence of asymmetric function, we develop a model for the transport cycle of degenerate ABC transporters. We will elaborate on the unclear functional advantages of a degenerate NBS.

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Crystal Structures of the MJ1267 ATP Binding Cassette Reveal an Induced-Fit Effect at the ATPase Active Site of an ABC Transporter

Cited by 284 publications

References 60 publications

The motor domains of ABC-transporters

The motor domains of ABC-transporters

ABC‐F translation factors: from antibiotic resistance to immune response

The role of the degenerate nucleotide binding site in type I ABC exporters

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