tailieunhanh - Báo cáo khoa học: by nucleotide affinity cleavage: a distinct nucleotide specificity of the C-terminal ATP-binding site

The 90-kDa heat shock protein (Hsp90) is a molecular chaperone that assists both in ATP-independent sequestra-tion of damaged proteins, and inATP-dependent folding of numerous targets, such as nuclear hormone receptors and protein kinases. Recent work from our lab and others has established the existence of a second, C-terminal nucleotide bindingsite besides the well characterized N-terminal, gel-danamycin-sensitive ATP-bindingsite. | Eur. J. Biochem. 270 2421-2428 2003 FEBS 2003 doi Comparative analysis of the ATP-binding sites of Hsp90 by nucleotide affinity cleavage a distinct nucleotide specificity of the C-terminal ATP-binding site Csaba Soti1 Akos Vermes1 Timothy A. J. Haystead2 and Peter Csermely1 1Department of Medical Chemistry Semmelweis University School of Medicine Budapest Hungary department of Pharmacology Cancer Biology Duke University Medical Center Durham North Carolina USA The 90-kDa heat shock protein Hsp90 is a molecular chaperone that assists both in ATP-independent sequestration of damaged proteins and in ATP-dependent folding of numerous targets such as nuclear hormone receptors and protein kinases. Recent work from our lab and others has established the existence of a second C-terminal nucleotide binding site beiides the well characlerieed N-temiinal gel-danamycin-sensitive ATP-binding The cryptic C-Ici - minal site becomes open only after the occupancy of the N-teiminal site. Our present work demonstrates the applicability of the oxidative nucleotide affinity cleavage in the site-specific characterization of nucleotide binding protems. We performed a systematic analysis of the nucleotide bindingspecificity of the Hsp90 nucleotide bindingsites. N-terminal bindingis specific to adenosine nucleotides with an intact adenine ring. Nicotinamide adenine dinucleotides and diadenosine polyphosphate alarmones are specific N-terminal nucleotides. The C-terminal bindingsite is much more unspecific it interacts with both purine and pirimi-dine nucleotides. Efficient binding to file C-lerrninal site requires both charged residues and a larger hydrophobic moiety. GTP and UTP are specific C-terminal nucleotides. 2 3 -ơ- 2 4 6-trinitrophenyl -nucleotides TNP-ATP TNP-GTP and pyrophosphate access the C-terminal bindingsite without the need for an occupied N-terminal site. Our data provide additional evidence for the dynamic domaindomain interactions of .

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