Correlation of Active Site Metal Content in Human Diamine Oxidase with Trihydroxyphenylalanine Quinone Cofactor Biogenesis,

Biochemistry ◽  
2010 ◽  
Vol 49 (38) ◽  
pp. 8316-8324 ◽  
Author(s):  
Aaron P. McGrath ◽  
Tom Caradoc-Davies ◽  
Charles A. Collyer ◽  
J. Mitchell Guss
Keyword(s):  
Active Site ◽  
Metal Content ◽  
Diamine Oxidase ◽  
Trihydroxyphenylalanine Quinone ◽  
Cofactor Biogenesis ◽  
Human Diamine Oxidase

scholarly journals The active site of purple acid phosphatase from sweet potatoes (Ipomoea batatas) . Metal content and spectroscopic characterization

1999 ◽  
Vol 260 (3) ◽  
pp. 709-716 ◽  
Author(s):  
Atila Durmus ◽  
Christoph Eicken ◽  
Bernd Horst Sift ◽  
Andreas Kratel ◽  
Reinhard Kappl ◽  
...  
Keyword(s):  
Acid Phosphatase ◽  
Active Site ◽  
Metal Content ◽  
Ipomoea Batatas ◽  
Spectroscopic Characterization ◽  
Purple Acid Phosphatase ◽  
Sweet Potatoes

scholarly journals Empirical Valence Bond Simulations Suggest a Direct Hydride Transfer Mechanism for Human Diamine Oxidase

ACS Omega ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. 3665-3674 ◽  
Author(s):  
Aleksandra Maršavelski ◽  
Dušan Petrović ◽  
Paul Bauer ◽  
Robert Vianello ◽  
Shina Caroline Lynn Kamerlin
Keyword(s):  
Diamine Oxidase ◽  
Valence Bond ◽  
Hydride Transfer ◽  
Transfer Mechanism ◽  
Empirical Valence Bond ◽  
Human Diamine Oxidase

scholarly journals Structure, Texture and Catalytic Properties of Pd/SiO2 Catalysts

1996 ◽  
Vol 13 (5) ◽  
pp. 423-431 ◽  
Author(s):  
S.A. El-Hakam ◽  
Awad I. Ahmed ◽  
S.M. Hassan ◽  
H.M. Farage
Keyword(s):  
Active Site ◽  
Metal Content ◽  
Catalytic Properties ◽  
Textural Properties ◽  
Nitrogen Adsorption ◽  
X Ray ◽  
Surface Areas ◽  
Dehydrogenation Of Cyclohexane ◽  
Adsorption Surface ◽  
Kinetics Of

The structural properties of Pd/silica catalysts have been investigated by means of DTA and X-ray techniques. The X-ray results indicate that Pd metal is the only phase formed. The textural properties were determined using low-temperature nitrogen adsorption. Surface areas were calculated and the dependence of the surface area on the metal content has been discussed. Pore structure analyses indicate the presence of both micro-and meso-pores. The dehydrogenation of cyclohexane was found to be affected by the metal content. The active site for the dehydrogenation process on Pd/silica catalysts consists of one Pd atom. The kinetics of the dehydrogenation exhibit a fractional order.

scholarly journals Heparin-binding motif mutations of human diamine oxidase allow the development of a first-in-class histamine-degrading biopharmaceutical

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Elisabeth Gludovacz ◽  
Kornelia Schuetzenberger ◽  
Marlene Resch ◽  
Katharina Tillmann ◽  
Karin Petroczi ◽  
...  
Keyword(s):  
Diamine Oxidase ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Binding Motif ◽  
Heparin Binding ◽  
Charged Amino Acids ◽  
New Treatment ◽  
Rats And Mice ◽  
Human Diamine Oxidase ◽  
Austrian Science Fund

<strong>Background:</strong> Excessive plasma histamine concentrations cause symptoms in mast cell activation syndrome, mastocytosis or anaphylaxis. Anti-histamines are often insufficiently efficacious. Human diamine oxidase (hDAO) can rapidly degrade histamine and therefore represents a promising new treatment strategy for conditions with pathological histamine concentrations. <strong>Results:</strong> Recombinant hDAO is rapidly cleared from the circulation in rats and mice. After replacement of positively charged amino acids of the heparin-binding motif with polar serine or threonine residues binding to heparin and heparan sulfate was strongly reduced. The double mutant rhDAO-R568S/R571T showed minimal cellular uptake. The short α-distribution half-life of the wildtype protein was eliminated and the clearance was significantly reduced in rodents. <strong>Conclusions: </strong>The successful decrease in plasma clearance of rhDAO by mutations of the heparin-binding motif with unchanged histamine-degrading activity represents the first step towards the development of rhDAO as a first-in-class biopharmaceutical to effectively treat diseases characterized by excessive histamine concentrations in plasma and tissues. <strong>Funding: </strong>Austrian Science Fund (FWF) Hertha Firnberg program grant T1135 (EG); ADD funding Sigrid Juselius Foundation, Medicinska Understödsförening Liv och Hälsa rft (TAS and SeV).

scholarly journals Mapping of the binding sites of human diamine oxidase (DAO) monoclonal antibodies

2017 ◽  
Vol 67 (3) ◽  
pp. 245-253 ◽  
Author(s):  
Hubert G. Schwelberger ◽  
Johannes Feurle ◽  
Gunnar Houen
Keyword(s):  
Monoclonal Antibodies ◽  
Binding Sites ◽  
Diamine Oxidase ◽  
Human Diamine Oxidase

scholarly journals A new crystal form of human diamine oxidase

2010 ◽  
Vol 66 (2) ◽  
pp. 137-142 ◽  
Author(s):  
Aaron P. McGrath ◽  
Kimberly M. Hilmer ◽  
Charles A. Collyer ◽  
David M. Dooley ◽  
J. Mitchell Guss
Keyword(s):  
Diamine Oxidase ◽  
Crystal Form ◽  
Human Diamine Oxidase

Human diamine oxidase cellular binding and internalization in vitro and rapid clearance in vivo are not mediated by N-glycans but by heparan sulfate proteoglycan interactions

Glycobiology ◽  
2020 ◽  
Author(s):  
Elisabeth Gludovacz ◽  
Kornelia Schuetzenberger ◽  
Marlene Resch ◽  
Katharina Tillmann ◽  
Karin Petroczi ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Cell Lines ◽  
Diamine Oxidase ◽  
Therapeutic Modality ◽  
Pharmacokinetic Data ◽  
Heparin Binding ◽  
Rapid Clearance ◽  
Human Diamine Oxidase

Abstract Human diamine oxidase (hDAO) rapidly inactivates histamine by deamination. No pharmacokinetic data are available to better understand its potential as a new therapeutic modality for diseases with excess local and systemic histamine, like anaphylaxis, urticaria or mastocytosis. After intravenous administration of recombinant hDAO to rats and mice, more than 90% of the dose disappeared from the plasma pool within 10 min. Human DAO did not only bind to various endothelial and epithelial cell lines in vitro, but was also unexpectedly internalized and visible in granule-like structures. The uptake of rhDAO into cells was dependent on neither the asialoglycoprotein-receptor (ASGP-R) nor the mannose receptor (MR) recognizing terminal galactose or mannose residues, respectively. Competition experiments with ASGP-R and MR ligands did not block internalization in vitro or rapid clearance in vivo. The lack of involvement of N-glycans was confirmed by testing various glycosylation mutants. High but not low molecular weight heparin strongly reduced the internalization of rhDAO in HepG2 cells and HUVECs. Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively. A docked heparin hexasaccharide interacted well with the predicted heparin binding site 568RFKRKLPK575. These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.

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