The Glu216/Ser218 pocket is a major determinant of spermine oxidase substrate specificity

2014 ◽  
Vol 461 (3) ◽  
pp. 453-459 ◽  
Author(s):  
Manuela Cervelli ◽  
Emanuela Angelucci ◽  
Pasquale Stano ◽  
Loris Leboffe ◽  
Rodolfo Federico ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Oxidase Activity ◽  
Major Determinant ◽  
Spermine Oxidase ◽  
Acetylpolyamine Oxidase ◽  
Specific Inhibitors

Mutation of spermine oxidase Glu216/Ser218 into the paralogue acetylpolyamine oxidase residues endows spermine oxidase with acetylpolyamine oxidase activity. Glu216 and Ser218 are major determinants of spermine oxidase substrate specificity. This finding will allow for the design of specific inhibitors for these enzymes.

scholarly journals Dual inhibitors of LSD1 and spermine oxidase

MedChemComm ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 778-790 ◽  
Author(s):  
Steven Holshouser ◽  
Matthew Dunworth ◽  
Tracy Murray-Stewart ◽  
Yuri K. Peterson ◽  
Pieter Burger ◽  
...  
Keyword(s):  
Spermine Oxidase ◽  
Dual Inhibitors ◽  
Acetylpolyamine Oxidase

Dual inhibitors of LSD1 and SMOX, with no activity against N1-acetylpolyamine oxidase (PAOX).

The 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity of human tyrosinase

2001 ◽  
Vol 354 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Concepción OLIVARES ◽  
Celia JIMÉNEZ-CERVANTES ◽  
José Antonio LOZANO ◽  
Francisco SOLANO ◽  
José Carlos GARCÍA-BORRÓN
Keyword(s):  
Carboxylic Acid ◽  
Substrate Specificity ◽  
Transient Expression ◽  
Oxidase Activity ◽  
Melanin Synthesis ◽  
Catalytic Activities ◽  
Human Melanocytes ◽  
Related Proteins ◽  
Rate Limiting ◽  
Human Tyrosinase

Melanin synthesis in mammals is catalysed by at least three enzymic proteins, tyrosinase (monophenol dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) and tyrosinase-related proteins (tyrps) 1 and 2, whose genes map to the albino, brown and slaty loci in mice, respectively. Tyrosinase catalyses the rate-limiting generation of l-dopaquinone from l-tyrosine and is also able to oxidize l-dopa to l-dopaquinone. Conversely, mouse tyrp1, but not tyrosinase, catalyses the oxidation of the indolic intermediate 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into the corresponding 5,6-indolequinone-2-carboxylic acid, thus promoting the incorporation of DHICA units into eumelanin. The catalytic activities of the human melanogenic enzymes are still debated. TYRP1has been reported to lack DHICA oxidase activity, whereas tyrosinase appears to accelerate DHICA consumption, thus raising the question of DHICA metabolism in human melanocytes. Here we have used two different approaches, comparison of the catalytic activities of human melanocytic cell lines expressing the full set of melanogenic enzymes or deficient in TYRP1, and transient expression of TYR and tyr genes in COS7 cells, to demonstrate that human tyrosinase actually functions as a DHICA oxidase, as opposed to the mouse enzyme. Therefore, human tyrosinase displays a broader substrate specificity than its mouse counterpart, and might be at least partially responsible for the incorporation of DHICA units into human eumelanins.

scholarly journals Polyamine catabolism and disease

2009 ◽  
Vol 421 (3) ◽  
pp. 323-338 ◽  
Author(s):  
Robert A. Casero ◽  
Anthony E. Pegg
Keyword(s):  
Dominant Role ◽  
Therapeutic Benefit ◽  
Spermine Oxidase ◽  
Polyamine Catabolism ◽  
Disease States ◽  
Disease Aetiology ◽  
Multiple Cell ◽  
Druggable Targets ◽  
Acetylpolyamine Oxidase ◽  
Insight Into

In addition to polyamine homoeostasis, it has become increasingly clear that polyamine catabolism can play a dominant role in drug response, apoptosis and the response to stressful stimuli, and contribute to the aetiology of several pathological states, including cancer. The highly inducible enzymes SSAT (spermidine/spermine N1-acetyltransferase) and SMO (spermine oxidase) and the generally constitutively expressed APAO (N1-acetylpolyamine oxidase) appear to play critical roles in many normal and disease processes. The dysregulation of polyamine catabolism frequently accompanies several disease states and suggests that such dysregulation may both provide useful insight into disease mechanism and provide unique druggable targets that can be exploited for therapeutic benefit. Each of these enzymes has the potential to alter polyamine homoeostasis in response to multiple cell signals and the two oxidases produce the reactive oxygen species H2O2 and aldehydes, each with the potential to produce pathological states. The activity of SSAT provides substrates for APAO or substrates for the polyamine exporter, thus reducing the intracellular polyamine concentration, the net effect of which depends on the magnitude and rate of any increase in SSAT. SSAT may also influence cellular metabolism via interaction with other proteins and by perturbing the content of acetyl-CoA and ATP. The goal of the present review is to cover those aspects of polyamine catabolism that have an impact on disease aetiology or treatment and to provide a solid background in this ever more exciting aspect of polyamine biology.

scholarly journals Development of Irreversible Inactivators of Spermine Oxidase and N1-Acetylpolyamine Oxidase

2014 ◽  
Vol 37 (3) ◽  
pp. 475-480 ◽  
Author(s):  
Shun-suke Moriya ◽  
Toshiyuki Miura ◽  
Koichi Takao ◽  
Yoshiaki Sugita ◽  
Keijiro Samejima ◽  
...  
Keyword(s):  
Spermine Oxidase ◽  
Acetylpolyamine Oxidase

Phenol oxidase activity of a monogenean, Paramazocraes thrissocles

1986 ◽  
Vol 60 (3) ◽  
pp. 234-238
Author(s):  
T. Thangaraj ◽  
A. Vinayakam ◽  
K. Nellaiappan
Keyword(s):  
Substrate Specificity ◽  
Metal Ions ◽  
Oxidase Activity ◽  
Phenol Oxidase ◽  
Maximum Activity ◽  
Ph Optimum ◽  
Phenol Oxidase Activity ◽  
Eggshell Formation ◽  
Chelating Compounds

AbstractThe phenol oxidase of a monogenean, Paramazocraes thrissocles, oxidizes phenolic amines more effectively than other phenols studied. Based on the substrate specificity, the probable substrate for eggshell formation has been suggested. The enzyme shows the pH optimum of 7–2. At 40°C it shows maximum activity. Proenzyme is activated by metal ions and detergents. Copper chelating compounds strongly inhibit the enzyme.

Role of Glycine 81 in (S)-Mandelate Dehydrogenase fromPseudomonas putidain Substrate Specificity and Oxidase Activity†

Biochemistry ◽  
2004 ◽  
Vol 43 (33) ◽  
pp. 10692-10700 ◽  
Author(s):  
Asteriani R. Dewanti ◽  
Yang Xu ◽  
Bharati Mitra
Keyword(s):  
Substrate Specificity ◽  
Oxidase Activity
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