Application of Native-State Electrospray Mass Spectrometry to Identify Zinc-Binding Sites on Engineered Hemoglobin

2000 ◽  
Vol 284 (2) ◽  
pp. 247-255 ◽  
Author(s):  
Julie Lippincott ◽  
Timothy J. Fattor ◽  
Douglas D. Lemon ◽  
Izydor Apostol
Keyword(s):  
Mass Spectrometry ◽  
Binding Sites ◽  
Electrospray Mass Spectrometry ◽  
Zinc Binding ◽  
Native State

scholarly journals Positive and negative nano-electrospray mass spectrometry of ruthenated serum albumin supported by docking studies: an integrated approach towards defining metallodrug binding sites on proteins

Metallomics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 587-594 ◽  
Author(s):  
Marija Nišavić ◽  
Goran V. Janjić ◽  
Amela Hozić ◽  
Marijana Petković ◽  
Miloš K. Milčić ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Serum Albumin ◽  
Binding Sites ◽  
Electrospray Mass Spectrometry ◽  
Integrated Approach ◽  
Docking Studies ◽  
Esi Ms ◽  
Negative Mode

Negative mode nanoLC/nano ESI MS was used for determing Ru(ii) binding sites on protein.

Covalent-Fragment Screening of Brd4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites

2019 ◽  
Author(s):  
Michael Olp ◽  
Daniel Sprague ◽  
Stefan Kathman ◽  
Ziyang Xu ◽  
Alexandar Statsyuk ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Binding Site ◽  
Binding Sites ◽  
Computational Prediction ◽  
Chemical Probes ◽  
Computational Docking ◽  
Fragment Screening ◽  
Covalent Inhibitors ◽  
Bet Protein ◽  
Proof Of Principle

<p>Brd4, a member of the bromodomain and extraterminal domain (BET) family, has emerged as a promising epigenetic target in cancer and inflammatory disorders. All reported BET family ligands bind within the bromodomain acetyl-lysine binding sites and competitively inhibit BET protein interaction with acetylated chromatin. Alternative chemical probes that act orthogonally to the highly-conserved acetyl-lysine binding sites may exhibit selectivity within the BET family and avoid recently reported toxicity in clinical trials of BET bromodomain inhibitors. Here, we report the first identification of a ligandable site on a bromodomain outside the acetyl-lysine binding site. Inspired by our computational prediction of hotspots adjacent to non-homologous cysteine residues within the <i>C</i>-terminal Brd4 bromodomain (Brd4-BD2), we performed a mid-throughput mass spectrometry screen to identify cysteine-reactive fragments that covalently and selectively modify Brd4. Subsequent mass spectrometry, NMR and computational docking analyses of electrophilic fragment hits revealed a novel ligandable site near Cys356 that is unique to Brd4 among all human bromodomains. This site is orthogonal to the Brd4-BD2 acetyl-lysine binding site as Cys356 modification did not impact binding of the pan-BET bromodomain inhibitor JQ1 in fluorescence polarization assays. Finally, we tethered covalent fragments to JQ1 and performed NanoBRET assays to provide proof of principle that this orthogonal site can be covalently targeted in intact human cells. Overall, we demonstrate the potential of targeting sites orthogonal to bromodomain acetyl-lysine binding sites to develop bivalent and covalent inhibitors that displace Brd4 from chromatin.</p>

Analysis of Trace Level Perchlorate in Drinking Water and Ground Water by Electrospray Mass Spectrometry

1998 ◽  
Author(s):  
Rebecca A. Clewell ◽  
Wayne T. Brashear ◽  
David T. Tsui ◽  
Sanwat Chaudhuri ◽  
Rachel S. Cassady
Keyword(s):  
Mass Spectrometry ◽  
Drinking Water ◽  
Ground Water ◽  
Electrospray Mass Spectrometry ◽  
Trace Level

Determination of the endogenous phosphorylation state of B-50/GAP-43 and neurogranin in different brain regions by electrospray mass spectrometry

FEBS Letters ◽  
1996 ◽  
Vol 389 (3) ◽  
pp. 309-313 ◽  
Author(s):  
Monica Di Luca ◽  
Lucia Pastorino ◽  
Vittorio Raverdino ◽  
Pierre N.E. De Graan ◽  
Antonio Caputi ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Mass Spectrometry ◽  
Brain Regions ◽  
Phosphorylation State

A polymeric microchip with integrated tips and in situ polymerized monolith for electrospray mass spectrometry

Lab on a Chip ◽  
2005 ◽  
Vol 5 (8) ◽  
pp. 869 ◽  
Author(s):  
Yanou Yang ◽  
Chen Li ◽  
Jun Kameoka ◽  
Kelvin H. Lee ◽  
H. G. Craighead
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Mass Spectrometry
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