Exploring the binding mode of semicarbazide-sensitive amine oxidase/VAP-1: identification of novel substrates with insulin-like activity

Journal of Medicinal Chemistry
Luc MartiA Zorzano

Abstract

We previously reported that substrates of semicarbazide-sensitive amine oxidase in combination with low concentrations of vanadate exert potent insulin-like effects. Here we performed homology modeling of the catalytic domain of mouse SSAO/VAP-1 and searched through chemical databases to identify novel SSAO substrates. The modeling of the catalytic domain revealed that aromatic residues Tyr384, Phe389, and Tyr394 define a pocket of stable size that may participate in the binding of apolar substrates. We identified a number of amines as substrates of human, rat, and mouse SSAO. The compounds PD0119035, 2,3-dimethoxy-benzylamine, and C-naphthalen-1-yl-methylamine showed high affinity as substrates of rat SSAO. C-Naphthalen-1-yl-methylamine was the only substrate that showed high affinity for human SSAO. C-Naphthalen-1-yl-methylamine and 4-aminomethyl-benzenesulfonamide showed the highest capacity to stimulate glucose transport in isolated rat adipocytes. The impact of these findings on the development of new treatments for diabetes is discussed.

References

Nov 1, 1986·Journal of Chemical Information and Computer Sciences·G W MilneM J Hammel
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
May 22, 1998·Journal of Molecular Biology·F Melo, E Feytmans
Nov 25, 1998·Protein Science : a Publication of the Protein Society·K MizuguchiJ P Overington
Dec 11, 1999·Nucleic Acids Research·A BatemanE L Sonnhammer
Jun 8, 2001·Journal of Computer-aided Molecular Design·T J EwingI D Kuntz
Nov 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·Nathalie MorinChristian Carpéné

❮ Previous
Next ❯

Citations

Sep 27, 2005·Journal of Physiology and Biochemistry·C CarpénéP Valet
Jan 19, 2013·Journal of Neural Transmission·Eva Bligt-LindénTiina Annamaria Salminen
Dec 7, 2013·Journal of Medicinal Chemistry·Eva Bligt-LindénTiina A Salminen
Dec 5, 2008·The Journal of Organic Chemistry·Ke-Qing Ling, Lawrence M Sayre
Dec 9, 2010·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Karin ErnbergJ Mitchell Guss
Jan 18, 2008·BMC Structural Biology·David PiedraXavier de la Cruz
Jun 17, 2011·Expert Opinion on Therapeutic Patents·Petra DunkelPéter Mátyus
Jan 30, 2007·Diabetes·Silvia García-VicenteAntonio Zorzano
May 4, 2017·World Journal of Diabetes·Christian CarpénéXavier Testar
Mar 7, 2009·ChemMedChem·Francesc YraolaMiriam Royo
Apr 9, 2009·Analytical and Bioanalytical Chemistry·Lemonia ValianouYannis Chryssoulakis
Apr 10, 2008·Analytical and Bioanalytical Chemistry·Erwin Rosenberg
Oct 3, 2009·Analytical and Bioanalytical Chemistry·Lemonia ValianouYannis Chryssoulakis
Mar 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Serhii VakalTiina A Salminen
Feb 28, 2009·Journal of Inorganic Biochemistry·Antonio ZorzanoSilvia García-Vicente

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.