Journal
RSC ADVANCES
Volume 10, Issue 63, Pages 38631-38639Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0ra06365g
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Funding
- JST, PRESTO, Japan [JPMJPR19G6]
- JSPS KAKENHI [16KT0055, 17H04866, 19H05781, 20H05453, 20H05448]
- Multidisciplinary Cooperative Research Program in CCS, University of Tsukuba
- HPCI system research project [hp190110]
- Equipex Equip@Meso project (Programme Investissements d'Avenir)
- CPER Alsacalcul/Big Data
- Grand Equipement National De Calcul Intensif (GENCI) [DARI-A0080906092]
- Grants-in-Aid for Scientific Research [20H05448, 20H05453, 16KT0055, 17H04866, 19H05781] Funding Source: KAKEN
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The oxidative deamination of biogenic amines, crucial in the metabolism of a wealth of living organisms, is catalyzed by copper amine oxidases (CAOs). In this work, on the ground of accurate molecular modeling, we provide a clear insight into the unique protonation states of the key catalytic aspartate residue Asp298 and the prosthetic group of topaquinone (TPQ) in the CAO of Arthrobacter globiformis (AGAO). This provides both extensions and complementary information to the crystal structure determined by our recent neutron diffraction (ND) experiment. The hybrid quantum mechanics/molecular mechanics (QM/MM) simulations suggest that the ND structure closely resembles a state in which Asp298 is protonated and the TPQ takes an enolate form. The TPQ keto form can coexist in the fully protonated state. The energetic and structural analyses indicate that the active site structure of the AGAO crystal is not a single state but rather a mixture of the different protonation and conformational states identified in this work.
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