QM/MM study of the conversion of biliverdin into verdoheme by heme oxygenase

• Published in: Theoretical chemistry accounts Vol. 138; no. 5; pp. 1 - 8
• Main Authors: Alavi, Fatemeh Sadat, Zahedi, Mansour, Safari, Nasser, Ryde, Ulf
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2019; Springer Nature B.V
• Subjects: Atomic/Molecular Structure and Spectra; Biliverdin; Chemical Sciences; Chemistry; Chemistry and Materials Science; Conversion; Exothermic reactions; Inorganic Chemistry; Iron; Kemi; Natural Sciences; Naturvetenskap; Organic Chemistry; Physical Chemistry; Potential energy; Quantum mechanical and molecular mechanical (QM/MM); Quantum mechanics; Regular Article; Teoretisk kemi; Teoretisk kemi (Här ingår: Beräkningskemi); Theoretical and Computational Chemistry; Theoretical Chemistry; Theoretical Chemistry (including Computational Chemistry); Verdoheme; Biliverdin; Verdoheme; Quantum mechanical and molecular mechanical (QM/MM)
• ISSN: 1432-881X; 1432-2234; 1432-2234
• DOI: 10.1007/s00214-019-2461-y

It has been shown that after production of oxophlorin, the first step of intermediate, both production of biliverdin and production of verdoheme occur simultaneously (Alavi et al. in Dalton Trans 47:8283–8291, 2018 ). So the mechanism that converts biliverdin into verdoheme is the subject of some controversy. The detailed conversion of verdoheme to biliverdin was demonstrated before by the Jerusalem group, using combined quantum mechanical and molecular mechanical (QM/MM) calculations. Conversion of iron biliverdin to iron verdoheme in the presence of H + was investigated using the B3LYP method and the def2-QZVP basis set, considering dispersion effects with the DFT-D3 approach, obtaining accurate energies with large QM regions of almost 1000 atoms. Two spin states, singlet and triplet, were considered for the conversion of biliverdin to verdoheme. The reactant and product are triplet and singlet in their ground states, respectively. The potential energy surface suggests that a spin inversion takes place during the course of reaction after TS2. The ring closing process is exothermic by 5.8 kcal/mol with a kinetic barrier of 16.5 kcal/mol. The activation barrier for removing OH from the ring to produce iron verdoheme is estimated to be 23.2 kcal/mol.