Crystallography of vitamin B12 proteins

Exploring the Implications of Vitamin B12 Conjugation to Insulin on Insulin Receptor Binding

“…Numerous additional considerations (such as the persistence of B 12 binding in the presence 422 www.chemmedchem.org of bulky groups or stronger surface interactions between the substituent and TCII that would attenuate the B 12 binding interaction strength) need to be addressed before a complete picture can be generated, but the observed accessibility does provide a structural basis for the success of previous bioconjugate studies, as noted elsewhere. [17] The TCII-B 12 -insulin complex is considered at two insulin geometries. In the first case, the crystal form of insulin is used as the geometry for the B 12 -insulin bioconjugate.…”

Untitled

“…Four of the six coordinations are provided by the corrin ring nitrogens, and a fifth by a dimethylbenzimidazole group. The sixth coordination partner varies, being a cyano group (-CN) (cyanocobalamin), a hydroxyl group (-OH) (hydroxocobalamin), a methyl group (-CH3) (methylcobalamin) or a 5'-deoxyadenosyl group (5-deoxyadenosylcobalamin) 5,6,7,8,9,10,11,12,13 . Most microorganisms, including bacteria and algae, synthesize vitamin B 12 , and they constitute the only source of the vitamin 14 .…”

Theoretical investigations of photophysics and spectroscopic properties in B12 cofactors.

“…They catalyze a variety of chemical processes that can be divided into two categories. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] The methyltransfer reactions, employing MeCbl, proceed by the heterolytic cleavage of the Co-C bond, leaving behind the methyl cation and cob(I)alamin. 19 In contrast, the radical-induced rearrangements or ribonucleotide reduction, utilizing AdoCbl, follows with a Co-C bond homolysis and production of an adenosyl radical and cob(II)alamin.…”

“…The significance of B 12 -dependent enzymes in vital processes is undeniable and therefore cobalamins have been vividly studied and discussed in the literature. 14,17,20,21,23,25,27,[31][32][33] However, only two MeCbl-and AdoCbl-based enzymes have been found in mammals. 34,35 Methionine synthase (MetH) is a methyltransferase that regenerates methionine (Met) from homocysteine (Hcy) by methyl group transfer.…”

“…34,35 Methionine synthase (MetH) is a methyltransferase that regenerates methionine (Met) from homocysteine (Hcy) by methyl group transfer. 23,25,27,32,33 This process is coupled with a demethylation of methyltetrahydrofolate (CH 3 -H 4 -folate) to tetrahydrofolate (H 4 -folate). Whereas Met is an essential aminoacid, H 4 -folate participates in the biosynthesis of amino acids, purine and pyrimidine and therefore is crucial for the synthesis of nucleic acids.…”