8eej: Difference between revisions
New page: '''Unreleased structure''' The entry 8eej is ON HOLD Authors: Description: Category: Unreleased Structures |
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==C. ammoniagenes monoamine oxidase (MAO) C424S variant bound to dopamine== | |||
<StructureSection load='8eej' size='340' side='right'caption='[[8eej]], [[Resolution|resolution]] 1.54Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8eej]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Corynebacterium_ammoniagenes Corynebacterium ammoniagenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8EEJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EEJ FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.54Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=LDP:L-DOPAMINE'>LDP</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8eej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8eej OCA], [https://pdbe.org/8eej PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8eej RCSB], [https://www.ebi.ac.uk/pdbsum/8eej PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8eej ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A807MR40_CORAM A0A807MR40_CORAM] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Monoamine oxidases (MAOs) play a key role in the breakdown of primary and secondary amines. In eukaryotic organisms, these enzymes are vital to the regulation of monoamine neurotransmitters and the degradation of dietary monoamines. MAOs have also been identified in prokaryotic species, although their role in these organisms is not well understood. Here, we report the biophysical and structural properties of a promiscuous, bacterial MAO from Corynebacterium ammoniagenes (caMAO). caMAO catalyzes the oxidation of a number of monoamine substrates including dopamine and norepinephrine, as well as exhibiting some activity with polyamine substrates such as cadaverine. The X-ray crystal structures of Michaelis complexes with seven substrates show that conserved hydrophobic interactions and hydrogen-bonding pattern (for polar substrates) allow the broad specificity range. The structure of caMAO identifies an unusual cysteine (Cys424) residue in the so-called "aromatic cage", which flanks the flavin isoalloxazine ring in the active site. Site-directed mutagenesis, steady-state kinetics in air-saturated buffer, and UV-vis spectroscopy revealed that Cys424 plays a role in the pH dependence and modulation of electrostatics within the caMAO active site. Notably, bioinformatic analysis shows a propensity for variation at this site within the "aromatic cage" of the flavin amine oxidase (FAO) superfamily. Structural analysis also identified the conservation of a secondary substrate inhibition site, present in a homologous member of the superfamily. Finally, genome neighborhood diagram analysis of caMAO in the context of the FAO superfamily allows us to propose potential roles for these bacterial MAOs in monoamine and polyamine degradation and catabolic pathways related to scavenging of nitrogen. | |||
Structural Insights into the Substrate Range of a Bacterial Monoamine Oxidase.,Muellers SN, Tararina MA, Kuzmanovic U, Galagan JE, Allen KN Biochemistry. 2023 Jan 20. doi: 10.1021/acs.biochem.2c00540. PMID:36662673<ref>PMID:36662673</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8eej" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monoamine oxidase|Monoamine oxidase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Corynebacterium ammoniagenes]] | |||
[[Category: Large Structures]] | |||
[[Category: Allen KN]] | |||
[[Category: Muellers SN]] | |||
Latest revision as of 13:20, 25 October 2023
C. ammoniagenes monoamine oxidase (MAO) C424S variant bound to dopamineC. ammoniagenes monoamine oxidase (MAO) C424S variant bound to dopamine
Structural highlights
FunctionPublication Abstract from PubMedMonoamine oxidases (MAOs) play a key role in the breakdown of primary and secondary amines. In eukaryotic organisms, these enzymes are vital to the regulation of monoamine neurotransmitters and the degradation of dietary monoamines. MAOs have also been identified in prokaryotic species, although their role in these organisms is not well understood. Here, we report the biophysical and structural properties of a promiscuous, bacterial MAO from Corynebacterium ammoniagenes (caMAO). caMAO catalyzes the oxidation of a number of monoamine substrates including dopamine and norepinephrine, as well as exhibiting some activity with polyamine substrates such as cadaverine. The X-ray crystal structures of Michaelis complexes with seven substrates show that conserved hydrophobic interactions and hydrogen-bonding pattern (for polar substrates) allow the broad specificity range. The structure of caMAO identifies an unusual cysteine (Cys424) residue in the so-called "aromatic cage", which flanks the flavin isoalloxazine ring in the active site. Site-directed mutagenesis, steady-state kinetics in air-saturated buffer, and UV-vis spectroscopy revealed that Cys424 plays a role in the pH dependence and modulation of electrostatics within the caMAO active site. Notably, bioinformatic analysis shows a propensity for variation at this site within the "aromatic cage" of the flavin amine oxidase (FAO) superfamily. Structural analysis also identified the conservation of a secondary substrate inhibition site, present in a homologous member of the superfamily. Finally, genome neighborhood diagram analysis of caMAO in the context of the FAO superfamily allows us to propose potential roles for these bacterial MAOs in monoamine and polyamine degradation and catabolic pathways related to scavenging of nitrogen. Structural Insights into the Substrate Range of a Bacterial Monoamine Oxidase.,Muellers SN, Tararina MA, Kuzmanovic U, Galagan JE, Allen KN Biochemistry. 2023 Jan 20. doi: 10.1021/acs.biochem.2c00540. PMID:36662673[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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