8een
From Proteopedia
(Difference between revisions)
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8een]] 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=8EEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EEN FirstGlance]. <br> | <table><tr><td colspan='2'>[[8een]] 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=8EEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EEN FirstGlance]. <br> | ||
| - | </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></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.46Å</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></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=8een FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8een OCA], [https://pdbe.org/8een PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8een RCSB], [https://www.ebi.ac.uk/pdbsum/8een PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8een ProSAT]</span></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=8een FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8een OCA], [https://pdbe.org/8een PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8een RCSB], [https://www.ebi.ac.uk/pdbsum/8een PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8een ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 13: | Line 14: | ||
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. | 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 | + | Structural Insights into the Substrate Range of a Bacterial Monoamine Oxidase.,Muellers SN, Tararina MA, Kuzmanovic U, Galagan JE, Allen KN Biochemistry. 2023 Feb 7;62(3):851-862. doi: 10.1021/acs.biochem.2c00540. Epub , 2023 Jan 20. PMID:36662673<ref>PMID:36662673</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 8een" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 8een" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Monoamine oxidase|Monoamine oxidase]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
C. ammoniagenes monoamine oxidase (MAO) C424S variant
| |||||||||||
