Histidine modification and monoamine oxidase activity
Published in bio.philica.com
Monoamine oxidase (MAO) is known to be susceptible to modification of histidine residues with loss of activity (Hiramatsu et al., 1975). Bovine liver MAO (predominantly MAO-B) inactivated by diethylpyrocarbonate (DEPC) could be restored with addition of hydroxylamine indicating histidine modification did not denature the enzyme. Later work suggested that both human MAO-A and MAO-B could be inactivated by DEPC (Jones, 2006).
Interestingly, imidazoline binding to monoamine oxidase is also inhibited by modifying histidine residues with DEPC or 4-bromophenacyl bromide (Limon-Boulez et al., 1996). With recent protein structure work showing imidazoline ligand binding in the entrance cavity of MAO-B (Bonivento et al., 2010) and a number of histidines (90, 91 & 115) located close to the 99-112 loop that shields the entrance cavity, it is tempting to assume that modifying one or more of these residues prevents access to the active site and the imidazoline binding site in MAO-B.
Unfortunately, histidine residues located near the entrance cavity in MAO-B are not conserved in MAO-A. The histidines corresponding to 91 & 115 in most mammalian MAO-B are often tyrosines in other MAO, histidine 90 is conserved in fish, bird and amphibian MAO sequences in addition to mammalian MAO-B sequences, but is replaced by glutamine in most MAO-A. Histidines may not be important for MAO activity, but with the (potential) ability to block access to both the entrance cavity and active site, histidine modification may be a useful tool in MAO-B research.
This is a general observation based on PhD work in Dr R Ramsay’s laboratory at the University of St Andrews, UK.
Bonivento D, Milczek EM, McDonald GR, Binda C, Holt A, Edmondson DE, Mattevi A (2010). Potentiation of ligand binding through cooperative effects in monoamine oxidase B. J Biol Chem. 285(47):36849-56.
Hiramatsu A, Tsurushiin S, Yasunobu KT (1975). Evidence for essential histidine residues in bovine-liver mitochondrial monoamine oxidase. Eur J Biochem. 57(2):587-93.
Jones TZE (2006). Monoamine Oxidase: Enzyme Inhibition by the Novel Antibacterial Oxazolidinones and Other Compounds. University of St Andrews thesis (Ph.D.).
Limon-Boulez I, Tesson F, Gargalidis-Moudanos C, Parini A (1996). I2-imidazoline binding sites: relationship with different monoamine oxidase domains and identification of histidine residues mediating ligand binding regulation by H+1. J Pharmacol Exp Ther. 276(2):359-64.
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Peer-review ratings as of 09:11:33 on 26th Sep 2017 (from 1 review, where a score of 100 is average):
Originality = 125.00, importance = 125.00, overall quality = 125.00
Published on Saturday 3rd September, 2011 at 14:49:25.
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The full citation for this Observation is:|
Jones, T. (2011). Histidine modification and monoamine oxidase activity. PHILICA.COM Observation number 70.
Peer review added 13th November, 2011 at 16:47:45
An interesting observation about histidine in MAO -A and -B.
On the other hand, the reversible change between the charged and uncharged states of the histidine residues acts like an electron transfer switch that is likely to be quite important for the mechanism of this enzyme’s catalytic action.
Because the pH changes close to the histidine residue pKa’s can be employed to modulate the reversible charging/discharging of the histidine residues a pH titration of histidine residues linked to the MOA’s enzyme activities should provide useful insights into the MOA’s enzymatic mechanisms.
Does the author have a more detailed plan of research with specific aims and tests?
added 24th November, 2011 at 10:45:09
In response to reviewer #47336, we have no plans for further work, although some pH work has been done.
Variations in activity and inhibition with pH: the protonated amine is the substrate for monoamine oxidase, but uncharged inhibitors bind better. Jones TZ, Balsa D, Unzeta M, Ramsay RR.
J Neural Transm. 2007;114(6):707-12. Epub 2007 Mar 31.