DFT and ONIOM(DFT:MM) studies on Co-C bond cleavage and hydrogen transfer in B 12-dependent methylmalonyl-coa mutase. stepwise or Concerted Mechanism?

Journal of the American Chemical Society

Volumn 131, Issue 14, 2009, Pages 5115-5125

  Li, Xin ^a,b,c   Chung, Lung Wa ^a,b,c   Paneth, Piotr ^a,b   Morokuma, Keiji ^a,b,c  

^a KYOTO UNIVERSITY   (Japan)

^b LODZ UNIVERSITY OF TECHNOLOGY   (Poland)

^c KYOTO UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CAGE EFFECT; CO-C BOND; CONCERTED MECHANISM; ENZYMATIC REACTION; GASPHASE; GEOMETRICAL DISTORTION; HYDROGEN TRANSFER; KEY FACTORS; METHYLMALONYL-COA MUTASE; QUANTUM MODELS; TRANSITION STATE;

GAS DYNAMICS; GASES; METHOD OF MOMENTS; PROBABILITY DENSITY FUNCTION; REACTION RATES;

HYDROGEN;

CARBON; COBALAMIN; COBALT; HYDROGEN; METHYLMALONYL COENZYME A MUTASE; ACYL COENZYME A; METHYLMALONYL-COENZYME A; SUCCINYL-COENZYME A;

ARTICLE; CHEMICAL BOND; CRYSTAL STRUCTURE; ENZYME STRUCTURE; GAS; HYDROGEN BOND; PROTEIN INTERACTION; PROTON TRANSPORT; QUANTUM MECHANICS; CHEMICAL STRUCTURE; CHEMISTRY; COMPUTER SIMULATION; ENZYME SPECIFICITY; KINETICS; METABOLISM; PROTEIN CONFORMATION; QUANTUM THEORY; THERMODYNAMICS; X RAY CRYSTALLOGRAPHY;

ACYL COENZYME A; COMPUTER SIMULATION; CRYSTALLOGRAPHY, X-RAY; HYDROGEN; KINETICS; METHYLMALONYL-COA MUTASE; MODELS, MOLECULAR; PROTEIN CONFORMATION; QUANTUM THEORY; SUBSTRATE SPECIFICITY; THERMODYNAMICS;

EID: 67849133632     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja807677z     Document Type: Article

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112. II states induced by the protein.
113. Glu370 forms two strong intermolecular hydrogen bonds with the ribose in I2, while it forms one intermolecular hydrogen bond in Rand I1. Also CoIII states R′and I1′with two intermolecular hydrogen bonds are calculated to be comparable in energy. R′is only higher than R by 0.5 kcal/mol. I′is a little lower than I1 by 0.1 kcal/mol (Figures S9).
114. These important interactions in the closed and reactive form of MMCM may partly explain the very small protein effect in the unreactive form in our previous calculations (ref 11), as Glu370 and Gln330 cannot form hydrogen bonds with the ribose in the unreactive form. It should be noted that only one carboxylic oxygen of Glu247 was found to interact with the ribose. Therefore, stabilization on the dissociated state by the protein in the unreactive form should be less than the reactive form.
115. Two other concerted transition states (TS′IC-IIIC and TS″IC-IIIC) with a different conformation of the ribose and different position of the substrate were also located. They are slightly higher in energy than TSIC-IIIC (Figure S13). In the gas phase, a very small imaginary frequency of 7i and 5i cm-1 was found in the Sub·/Arg and IIIC, respectively.
116. The electrostatic interaction is estimated from the energy of the whole QM system subtracting the total energy for completely separating the QM part of the corrin ring and the imidazole from the rest of the QM parts. The electrostatic interaction with the corrin ring and the imidazole is roughly-15.4 kcal/mol for TSIC-IIIC and-6.2 kcal/mol for TSI2-I3. It should be noted that the above-mentioned electrostatic interactions are overestimated, particularly for TSIC-IIIC, as the isolated fragments are not relaxed.
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123. In terms of Ä EQM, the reaction barrier and energy for the hydrogen transfer relative to I2 in the protein are similar to those relative to the isolated intermediates II to III in the gas phase.
124. For GluMut, the calculated Co · · · C5′distance in the concerted transition state is ∼3.23 Å in the gas phase (ref 10b), which is similar to that for the bond dissociated state for conformation B in the crystal structure (3.17 Å) and in the QM/MM study 3.48 Å (refs 10d and 34).
125. According to G2(MP2) calculations, the hydrogen transfer reaction from the substrate (Sub) to the Ado radical (Ado·) is slightly exothermic by 3.3 kcal/mol (without ZPC) Curtiss, L. A.; Raghavachari, K.; Pople, J. A. J. Chem. Phys. 1993, 98, 1293.
126. The spin densities of Co, C5′, and Csub for the key ONIOM-optimized structures are shown in Table S8 of the Supporting Information.
127. As shown in Figure S13, the concerted transition state TS″IC-IIIC with the shortest Co · · ·C bond (3.57 Å) was calculated to be the least favorable concerted transition state. Therefore, in addition to the stabilization by the presence of the cob(II)alamin, the energetics of the transition state was shown to be also influenced by other factors (such as hydrogen bonding and conformation of the ribose).