MethylmalonylCoAMutase

Abstract

The 5′‐adenosylcobalamin dependent methylmalonyl‐CoA mutase (MCM) catalyzes the reversible and stereospecific equilibration of ( 2R )‐methylmalonyl CoA and succinyl CoA through a radical mechanism. Its occurrence ranges from bacteria to mammals, where it is required for the metabolism or biosynthesis of propionate. MCM from Propionibacterium shermanii is an αβ‐heterodimer of total molecular weight 150 kDa, containing an inactive β‐subunit along with an active α‐subunit, the latter binding one adenosylcobalamin molecule close to the active site. The protein was found to occur in two fundamentally different conformations: in the presence of substrates it crystallizes in a “closed” conformation, whereas in the absence of substrates an “open” conformation is observed. This dramatic conformational change suggests a mechanism for the first step of the MCM‐catalyzed reaction cycle, i.e. the substrate‐induced homolysis of the Co–C bond.

Combined Spectroscopic/Computational Studies of Vitamin B12 Precursors: Geometric and Electronic Structures of Cobinamides

“…AdoCbl and MeCbl are best known for participating in the catalytic mechanisms of carbon skeleton isomerases 9 and methyltransferases, respectively, serving as essential cofactors for enzymes such as methylmalonyl-CoA mutase, 10, 11 glutamate mutase, 12–14 dioldehydratase, 15, 16 and methionine synthase. 17, 18 Alternatively, cobinamides are key intermediates in the de novo biosynthetic pathway of biologically active cobalamins in lower organisms, acting as substrates for enzymes such as the Co 1+ corrinoid:ATP adenosyltransferases.…”

“…While the corrinoid cofactors are of significant interest to chemists due to their complex geometric and electronic structures, the vital roles they play in biological systems have also caught the attention of biologists and biochemists. AdoCbl and MeCbl are best known for participating in the catalytic mechanisms of carbon skeleton isomerases and methyltransferases, respectively, serving as essential cofactors for enzymes such as methylmalonyl-CoA mutase, , glutamate mutase, − dioldehydratase, , and methionine synthase. , Alternatively, cobinamides are key intermediates in the de novo biosynthetic pathway of biologically active cobalamins in lower organisms, acting as substrates for enzymes such as the Co 1+ corrinoid:ATP adenosyltransferases. − In addition, cobinamides are extremely useful for investigating the function of the lower axial ligand in base-off/His-on cobalamin-dependent enzymes (e.g., methylmalonyl-CoA mutase , ) and can serve as interesting analogues to study enzymes that bind the cobalamin cofactors in the base-off/His-off fashion (e.g., the corrinoid iron–sulfur protein in methanogens − ).…”

Biosynthesis of 2-hydroxyisobutyric acid (2-HIBA) from renewable carbon

“…The so-called 2-hydroxyisobutyryl-CoA mutase is a new representative of the CoA-carbonyl mutase family. These enzymes catalyze the 1,2-rearrangement of the CoA-activated carboxyl group in the carbon skeleton of their substrates [40,41] (Figure 4). In this quite complicated reaction, the cofactor adenosylcobalamin is used to create radical intermediates.…”

Kinetics and mechanism of oxidation of super-reduced cobalamin and cobinamide species by thiosulfate, sulfite and dithionite

“…Co 3+ -and Co 2+ -Cbls are found in isomerases (e.g., methylmalonyl-CoA mutase), and Co 3+ -and Co 1+ -Cbls participate in catalytic cycles of methyltransferases (e.g., methionine synthase) and some other enzymes. [1][2][3][4][5][6] The oxidation state of the cobalt ion in Cbls directly influences the compound's coordination and redox behavior, with a lower cobalt oxidation state decreasing the possible number of ligands. Co 3+ -cobalamins (Cbl(III)) exist as six-coordinate complexes, Co 2+ -cobalamins (Cbl(II)) are predominantly fivecoordinated (with the exception of six-coordinate complexes with SO 2 − anion-radical 7 and thiocyanate 8 ), and Co 1+ -cobalamin (Cbl(I)) is four-coordinated.…”