“…The CNCbl monocarboxylic acid isomers have also been used in studies of the interaction of CNCbl with intrinsic factor (Lien et al, 1974;Ellenbogen, 1975) and the transport of vitamin B12 (Kensley et al, 1978). In the intrinsic factor study (Lien et al, 1974) the binding of CNCbl lactone was compared to the binding of what was thought to be the d acid isomer.…”
Section: Discussionmentioning
confidence: 99%
“…In the study on transport of vitamin B12 in Escherichia coli (Kensley et al, 1978) it was found that the three monocarboxylic acids and their derivatives gave different dissociation constants for the different isomers of the same derivative as determined by competition with CN[3H]Cbl in binding to the receptor. The major conclusions were reinterpreted by one of the authors (Bradbeer, 1982) in light of the reassignments of the acid isomers by Anton et al (1980).…”
Section: Discussionmentioning
confidence: 99%
“…It was speculated that steric effects and/or lack of hydrogen-bond donation from the analogues formed a "looser" complex with the apoenzyme making the breakage of the Co-C bond less energetically favorable. The interpretation of this and other experiments (Morley et al, 1968;Yakusheva et al, 1977;Kensley et al 1978;Lien et al, 1974; Ellenbogen, 1975) involving the modification of the propionamide side chains depends on the assignment of the three cyanocobalaminmonocarboxylic acid isomers that are used as a starting point for further modifications.…”
The three cyanocobalaminmonocarboxylic acid isomers known to be produced by the mild acid hydrolysis of the b-, d-, and e-propionamide side chains of vitamin B12 have been unambiguously assigned by modern 2D NMR methods. Previously, structural assignments had been made by less definitive NMR methods, and both X-ray and neutron diffraction studies had failed to locate unambiguously the position of the carboxyl group. The b and e isomers were structurally assigned in this study, on the basis of the assignment of the 13C NMR signal of the carboxyl group from HMBC (1H-detected heteronuclear multiple-bond correlation) spectra. The carboxyl group resonances exhibited the greatest changes in chemical shift between the protonated (pH 2) and deprotonated (pH greater than 7) forms of the acids. The d isomer was assigned by difference. Since the HMBC experiments required the assignments of side-chain CH2 signals, homonuclear Hartmann-Hahn, 2D homonuclear correlation, 2D nuclear Overhauser effect, 1H-detected heteronuclear multiple quantum coherence, and HMBC spectroscopies were used to assign completely the 1H and 13C NMR spectra of the b and e isomers at pH approximately 7. By comparison with the 13C NMR spectra of the b and e isomers, nearly one-fourth of the resonances of the 13C NMR spectrum of vitamin B12 have been reassigned. The sites of incorporation of 13C-labeled precursors in B12 biosynthesis found in previous studies have been verified by a comparison of 13C assignments. The results of studies using cobalamins modified at the b-, d-, and e-propionamide side chains in which the incorrect structural assignments were used (before 1980), particularly studies of B12-dependent enzymes, require reinterpretation using the correct structural assignments.
“…The CNCbl monocarboxylic acid isomers have also been used in studies of the interaction of CNCbl with intrinsic factor (Lien et al, 1974;Ellenbogen, 1975) and the transport of vitamin B12 (Kensley et al, 1978). In the intrinsic factor study (Lien et al, 1974) the binding of CNCbl lactone was compared to the binding of what was thought to be the d acid isomer.…”
Section: Discussionmentioning
confidence: 99%
“…In the study on transport of vitamin B12 in Escherichia coli (Kensley et al, 1978) it was found that the three monocarboxylic acids and their derivatives gave different dissociation constants for the different isomers of the same derivative as determined by competition with CN[3H]Cbl in binding to the receptor. The major conclusions were reinterpreted by one of the authors (Bradbeer, 1982) in light of the reassignments of the acid isomers by Anton et al (1980).…”
Section: Discussionmentioning
confidence: 99%
“…It was speculated that steric effects and/or lack of hydrogen-bond donation from the analogues formed a "looser" complex with the apoenzyme making the breakage of the Co-C bond less energetically favorable. The interpretation of this and other experiments (Morley et al, 1968;Yakusheva et al, 1977;Kensley et al 1978;Lien et al, 1974; Ellenbogen, 1975) involving the modification of the propionamide side chains depends on the assignment of the three cyanocobalaminmonocarboxylic acid isomers that are used as a starting point for further modifications.…”
The three cyanocobalaminmonocarboxylic acid isomers known to be produced by the mild acid hydrolysis of the b-, d-, and e-propionamide side chains of vitamin B12 have been unambiguously assigned by modern 2D NMR methods. Previously, structural assignments had been made by less definitive NMR methods, and both X-ray and neutron diffraction studies had failed to locate unambiguously the position of the carboxyl group. The b and e isomers were structurally assigned in this study, on the basis of the assignment of the 13C NMR signal of the carboxyl group from HMBC (1H-detected heteronuclear multiple-bond correlation) spectra. The carboxyl group resonances exhibited the greatest changes in chemical shift between the protonated (pH 2) and deprotonated (pH greater than 7) forms of the acids. The d isomer was assigned by difference. Since the HMBC experiments required the assignments of side-chain CH2 signals, homonuclear Hartmann-Hahn, 2D homonuclear correlation, 2D nuclear Overhauser effect, 1H-detected heteronuclear multiple quantum coherence, and HMBC spectroscopies were used to assign completely the 1H and 13C NMR spectra of the b and e isomers at pH approximately 7. By comparison with the 13C NMR spectra of the b and e isomers, nearly one-fourth of the resonances of the 13C NMR spectrum of vitamin B12 have been reassigned. The sites of incorporation of 13C-labeled precursors in B12 biosynthesis found in previous studies have been verified by a comparison of 13C assignments. The results of studies using cobalamins modified at the b-, d-, and e-propionamide side chains in which the incorrect structural assignments were used (before 1980), particularly studies of B12-dependent enzymes, require reinterpretation using the correct structural assignments.
“…Corrinoid transport loci in the Bacteroidetes have components homologous to those in Escherichia coli, including an outer membrane transporter (BtuB), periplasmic binding protein (BtuF), and inner membrane ATP-dependent transporters (BtuC/D) (Di Girolamo and Bradbeer, 1971;Kenley et al, 1978). Unlike E. coli, Bacteroidetes transport operons also include a novel family of surface-exposed lipoproteins (BtuG), critical for binding extracellular corrinoids and essential for efficient transport via BtuB (Wexler et al, 2018).…”
Highlights d Diverse mobile genetic elements in gut microbes encode vitamin B 12 transporters d Transfer of CTns with B 12 transporters complement transport-deficient strains d CTns with B 12 transporters offer competitive advantages during in vitro growth d In vivo conjugation restores ability to use B 12 in transportdeficient Bacteroides
“…The six carboxamide corrin ring substituents provide polar hydrogen bond donating and accepting functionalities which are potential points of binding interactions with the various types of proteins that bind Cbls. Analogs with structurally altered peripheral substituents have consequently been used to study the structural basis of Cbl binding to vitamin B 12 binding proteins, − vitamin B 12 transport receptors, , and 5‘-deoxyadenosylcobalamin- (AdoCbl 1 -) requiring enzymes. − In addition, recent work has suggested that steric interference with side chain thermal motions by the organic ligand of RCbls can provide significant entropic driving force for cleavage of the Co−C bonds in such complexes . Analogs of CNCbl 1 ( 1 ) in which the b , c , d , or e amide side chain is hydrolyzed to a carboxylic acid are well-known and well-characterized, ,− as are the N -alkyl amides and alkyl esters produced from them. ,, …”
Treatment of the c-monocarboxylate of
cyanocobalamin with diphenylphosphoryl azide affords the
c-NH2 derivative in moderate yield along with a
novel green corrinoid. The latter is also obtained when the amine
is treated with aqueous base. A single-crystal X-ray diffraction
analysis shows that the green corrinoid lacks a c side chain
and contains a C7−C8 double bond indicating that the B pyrrole ring
has been aromatized.
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