The crystal structure of human adenylate kinase 6: An adenylate kinase localized to the cell nucleus

Ren, Hai; Wang, Liya; Bennett, Matthew; Liang, Yu-He; Zheng, Xiaofeng; Lu, Fei; Li, Lanfen; Nan, Jie; Luo, Ming; Eriksson, Staffan; Zhang, Chuanmao; Su, Xiaodong

doi:10.1073/pnas.0407459102

Cited by 83 publications

(85 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AK (ATP:AMP phosphotransferase, EC 2.7.4.3) has a molecular weight of 21-23 kDa. There are at least five major families of AK: AK1 is from the cytosol of mammalian or vertebrate muscles, AK2 is located in the mammalian mitochondrial intermembrane, AK3 is from the mammalian mitochondrial matrix, AKe is found in Escherichia coli, AKy is generated by Saccharomyces cerevisiae [27], and a recently reported AK6 minor family in cell nucleus [32]. The ATP binding sites of AK have been studied in many different AK families, including chicken, human, porcine, rabbit AK1, and AKe.…”

Section: Resultsmentioning

confidence: 99%

Elucidating the site of protein-ATP binding by top-down mass spectrometry

Yin

Loo

2010

J. Am. Soc. Mass Spectrom.

101

View full text Add to dashboard Cite

A Fourier-transform ion cyclotron resonance (FT-ICR) top-down mass spectrometry strategy for determining the adenosine triphosphate (ATP)-binding site on chicken adenylate kinase is described. Noncovalent protein-ligand complexes are readily detected by electrospray ionization mass spectrometry (ESI-MS), but the ability to detect protein-ligand complexes depends on their stability in the gas phase. Previously, we showed that collisionally activated dissociation (CAD) of protein-nucleotide triphosphate complexes yield products from the dissociation of a covalent phosphate bond of the nucleotide with subsequent release of the nucleotide monophosphate (Yin, S. et al., J. Am. Soc. Mass Spectrom. 2008, 19, 1199 -1208. The intrinsic stability of electrostatic interactions in the gas phase allows the diphosphate group to remain noncovalently bound to the protein. This feature is exploited to yield positional information on the site of ATP-binding on adenylate kinase. CAD and electron capture dissociation (ECD) of the adenylate kinase-ATP complex generate product ions bearing monoand diphosphate groups from regions previously suggested as the ATP-binding pocket by NMR and crystallographic techniques. Top-down MS may be a viable tool to determine the ATP-binding sites on protein kinases and identify previously unknown protein kinases in a functional proteomics study. (J Am Soc Mass Spectrom 2010, 21, 899 -907) © 2010 American Society for Mass Spectrometry P roteins function in biology through direct interaction with other molecules. A ligand can be a molecule, an atom, or an ion that binds to a specific site on the protein by a variety of means, including hydrogen bonding, Van der Waals interactions, and ionic forces. Determining the presence of protein-ligand interactions and the structures of proteinligand complexes are of critical importance in biology, and this knowledge is often essential for efforts to establish new molecular drug targets and to develop more potent medicines.A number of biophysical tools are available to characterize the interaction between a protein and its ligand(s). However, mass spectrometry (MS) offers potential advantages in sensitivity, specificity, and speed, especially compared with high-resolution nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography. With electrospray ionization (ESI) to ionize macromolecules without disrupting covalent bonds while maintaining weak noncovalent interactions, the ESI-MS molecular mass measurement provides direct evidence for protein-ligand associations. The proteinligand interactions are often sufficiently retained upon the transition from solution to the gas phase that the complex size and binding stoichiometry can be measured [1][2][3].Although binding stoichiometry and, in many examples, the relative and absolute solution binding affinities can be measured by ESI-MS methodologies, determining the precise ligand binding site on a target protein is not easily tractable using MS directly. Tandem mass spectrometry (MS/MS) is widely applied...

show abstract

Section: Resultsmentioning

confidence: 99%

Elucidating the site of protein-ATP binding by top-down mass spectrometry

Yin

Loo

2010

J. Am. Soc. Mass Spectrom.

101

View full text Add to dashboard Cite

show abstract

“…Fap7 contains the Walker A and B sequence elements of an ATPase but structurally resembles an adenylate kinase (AK) (8,9). A weak NTPase and a nucleotide kinase activity have been demonstrated for the human protein in vitro (8,9). Fap7 was shown to bind specifically to ribosomal protein Rps14 and to transiently associate with preribosomal complexes at multiple points during the biogenesis pathway (10).…”

mentioning

confidence: 99%

“…One peculiar example for such a factor is a protein called Fap7 in Saccharomyces cerevisiae (6) and cofilin interacting protein (hCINAP) or adenylate kinase 6 (hADK6) in humans (7). Fap7 contains the Walker A and B sequence elements of an ATPase but structurally resembles an adenylate kinase (AK) (8,9). A weak NTPase and a nucleotide kinase activity have been demonstrated for the human protein in vitro (8,9).…”

mentioning

confidence: 99%

Essential ribosome assembly factor Fap7 regulates a hierarchy of RNA–protein interactions during small ribosomal subunit biogenesis

Hellmich¹,

Weis²,

Lioutikov³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significance Ribosomes are complex macromolecular machines universal to all domains of life that synthesize all cellular proteins. They consist of many different protein and RNA building blocks. Their biogenesis—a paradigm for the assembly of macromolecular machines in general—is a highly complex and tightly regulated process in eukaryotes requiring the concerted action of many ribosome assembly factors. In this study we analyze the cross-talk between two of these assembly factors and ribosomal building blocks with biophysical methods and show how it might contribute to the fidelity and efficiency of ribosome assembly.

show abstract

“…1). Both ATPase and AK activities have been demonstrated for AD-004 (16,19). Nuclear localization of AD-004 may depend upon its interaction with coilin, a major protein component of Cajal bodies (19,20).…”

mentioning

confidence: 99%

“…The defining member of the nuclear-localized AK group is human AD-004 (CINAP; AK-6), and its crystal structure has been determined (16). The positions of the P-loop, the NMPbinding domain, and the lid domain are indicated in the Hbr1p primary sequence (Fig.…”

mentioning

confidence: 99%

ATP Binding to Hemoglobin Response Gene 1 Protein Is Necessary for Regulation of the Mating Type Locus in Candida albicans

Peterson

Pendrak

Roberts

2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

HBR1 (hemoglobin response gene 1) is an essential gene inCandida albicans that positively regulates mating type locus MTL␣ gene expression and thereby regulates cell type-specific developmental genes. Hbr1p contains a phosphate-binding loop (P-loop), a highly conserved motif characteristic of ATP-and GTP-binding proteins. Recombinant Hbr1p was isolated in an oligomeric state that specifically bound ATP with K d ϳ2 M. ATP but not ADP, AMP, GTP, or dATP specifically protected Hbr1p from proteolysis by trypsin. Site-directed mutagenesis of the highly conserved P-loop lysine (K22Q) and the less conserved glycine (G19S) decreased the binding affinity for soluble ATP and ATP immobilized through its ␥-phosphate. ATP bound somewhat more avidly than ATP␥S to wild type and mutant Hbr1p. Although Hbr1p exhibits sequence motifs characteristic of adenylate kinases, and adenylate kinase and ATPase activities have been reported for the apparent human ortholog of Hbr1p, assays for adenylate kinase activity, autophosphorylation, and ATPase activity proved negative. Overexpression of wild type but not the mutant forms of Hbr1p restored MTl␣2 expression in an HBR1/hbr1 mutant, indicating that ATP binding to the P-loop is necessary for this function of Hbr1p.

show abstract

The crystal structure of human adenylate kinase 6: An adenylate kinase localized to the cell nucleus

Cited by 83 publications

References 33 publications

Elucidating the site of protein-ATP binding by top-down mass spectrometry

Elucidating the site of protein-ATP binding by top-down mass spectrometry

Essential ribosome assembly factor Fap7 regulates a hierarchy of RNA–protein interactions during small ribosomal subunit biogenesis

ATP Binding to Hemoglobin Response Gene 1 Protein Is Necessary for Regulation of the Mating Type Locus in Candida albicans

Contact Info

Product

Resources

About