QM−MM Study of Nitrite Reduction by Nitrite Reductase of Pseudomonas aeruginosa

• DOI: 10.1021/jp048807r
• Publication Date: 2004-11-11T07:12:58Z
• Authors: Marcelo A. Martí; Alejandro Crespo; Sara E. Bari; Fabio A. Doctorovich; Darío A. Estrin
• Keywords: 0301 basic medicine; 03 medical and health sciences

The one electron reduction of nitrite to NO, catalyzed in vivo by a group enzymes called reductases (NIRs), has been extensively investigated due its relevance the processes denitrification. heme containing NIRs are soluble noncovalent homodimers with two groups each subunit: d1 heme, site reduction, and type c responsible for internal transfer. High resolution X-ray structures show that all have distal histidines active as common feature. We analyzed reaction mechanism Pseudomonas aeruginosa (Pa) NIR using combined quantum mechanics/molecular mechanics (QM−MM) approach. central Fe(II) porphyrin complex plus proximal were treated at density functional theory level, while solvated protein environment was modeled Amber force field. Our results indicate binds reduced histidine protonated that, after protonation second histidine, proton transfer dehydration result an FeIII(NO) species free water molecule coordinated both histidines. computed also suggest NO ligand is probably displaced another cavity. enzyme finally recovers resting state, reorganization, formation. catalytic capacity lies primarily on histidines, real guards