Coenzyme B12 chemistry: the crystal and molecular structure of cob(II)alamin

Kraeutler, Bernhard; Keller, Walter; Kratky, Christoph

doi:10.1021/ja00206a037

Cited by 158 publications

(167 citation statements)

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“…125 mg (82.4%) were recovered and were subsequently dissolved in 5 ml deoxygenated H 2 O in a glovebox (Mecaplex, Switzerland; N 2 atmosphere, <15 parts per million O 2 ). Catalytic reduction was performed with platinum oxide as catalyst at 101 325 Pa H 2 as described in Kra È utler et al (1989).…”

Section: Preparation and Crystallizationmentioning

confidence: 99%

“…However, comparison of the crystal structure of B 12r (Kra È utler et al, 1989) with that of the coenzyme (Lenhert & Hodgkin, 1961;Lenhert, 1968) reveals no major molecular distortion which would explain the observed CoÐC bond weakening. It was therefore suggested that the CoÐC bond is labilized by way of enzyme-induced separation of the homolysis fragments by strong differential binding of the separated fragments to the enzyme (Kra È utler et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

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Neutron Laue diffraction studies of coenzyme cob(II)alamin

Langan

Lehmann

Wilkinson

et al. 1999

Acta Crystallogr D Biol Cryst

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Using a recently designed neutron single-crystal diffractometer utilizing a narrow-band Laue concept (LADI), diffraction data were collected from a crystal of the coenzyme cob(II)alamin (B 12r ), crystallized from a mixture of D 2 O and perdeuterated acetone. The instrument was placed at the end of a cold neutron guide at the Institute Laue Langevin (ILL, Grenoble, France), and data collection with neutrons of 1.8± 8.0 A Ê wavelength to a crystallographic resolution of 1.43 A Ê was complete after about 36 h. This compares favourably with a previous experiment utilizing the same crystal specimen, where more than four weeks were required to collect monochromatic diffraction data to about 1 A Ê resolution. Using the Laue data, the structure was solved by molecular replacement with the known X-ray crystal structure. Difference density maps revealed the atomic positions (including deuterium atoms) of seven ordered solvent water molecules and two (partially disordered) acetone molecules. These density maps were compared with corresponding maps computed with monochromatic neutron-diffraction data collected to 1.0 A Ê resolution using the same crystal specimen, as well as to maps derived from high-resolution (0.90 A Ê ) synchrotron X-ray data. In spite of the better de®nition of atomic positions in the two high-resolution maps, the 1.43 A Ê LADI maps show considerable power for the determination of the location of hydrogen and deuterium positions.

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Section: Preparation and Crystallizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neutron Laue diffraction studies of coenzyme cob(II)alamin

Langan

Lehmann

Wilkinson

et al. 1999

Acta Crystallogr D Biol Cryst

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“…Moreover, base-off methylcob(II)alamin compound cannot be considered in Co-C bond cleavage reaction of bio-reactions since is predicting a four coordinate vitamin B 12 specie immediately after a Co-C bond cleavage of methylcobalamin compound [39,68,106]. Instead, several experimental results show that methylco(II)calamine cofactor is fi ve coordinate [23][24][25][26][27][28]101,102] immediately after Co-C bond cleavage. Another unfortunate discrepancy is that theoretical results support the existence of a six-coordinate methylcobal(II)aminecofactor with dimethybenzimidazol ligand bonded to cobalt ion.…”

Section: Density Functional Theory (Dft) and Quantum Mechanics/ Molecmentioning

confidence: 99%

The Nature of the Co-C Bond Cleavage Processes in Methylcob(II)Alamin and Adenosylcob(III)Alamin

Spataru¹,

Fernández²

2016

ChemJMold

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Abstract. Unfortunately, there are still signifi cant disagreements between experimental and theoretical data of rate constants, energy barriers for Co-C bond cleavage process and coordination numbers of vitamin B 12 coenzyme species in spite of the remarkable efforts done by research community. Therefore, no grounded mechanisms for Co-C vitamin B 12 coenzyme bond breaking process and subsequent reactions have been found up to now. The infl uence of the mixing orbitals e.g. Pseudo-Jahn-Teller and similar effects on the reactions paths of bond-cleavage mechanisms of vitamin B 12 co-factors must be taken into account by utilizing multi-reference methods, in particular multiconfi gurational self-consistent fi eld (MCSCF) method. Then, the change in total energy along the normal coordinate Q for the stretching mode including Co-C and Co-N bonds in vitamin B 12 cofactors is expected due to a "vibronic" coupling term, which couples an excited state and ground state by a second order derivative potential-energy operator. The strong state mixing effect is expected to lead to low energy barriers and to Co-C and Co-N axial bond cleavage events in agreement with experimental data. Afterward, the updated mechanisms of vitamin B 12 bio-processes can be determined.Keywords: vitamin B 12 , mechanism, bio-catalysis, Pseudo-Jahn-Teller effect, DFT, MCSCF. Received: December 2015/ Revised fi nal: February 2016/ Accepted: February 2016 IntroductionVitamin B 12 cofactor is one of eight B vitamins and is involved in mammalian cellular metabolism, infl uencing amino acid and DNA synthesis [1] and hematopoiesis. The best known human physiological function of vitamin B 12 is its role in promoting normal health in the brain and nervous system. Vitamin B 12 anemia can cause such neurologic dysfunction as weakness, fatigue, light-headedness, rapid heartbeat, rapid breathing, pale skin color, bruising, and bleeding (including bleeding gums). The more severe vitamin B 12 anemia dysfunctions are characterized by tingling or numbness of the fi ngers and toes, diffi culty walking, mood changes, depression, memory loss, disorientation and, in most severe cases, dementia [2]. Vitamin B 12 defi ciency has even been considered in playing a role in the development of Alzheimer's disease [3][4][5][6][7].The vitamin B 12 cofactor contains a cobalt atom surrounded by an equatorial corrin ring. Covalently linked to the central atom is a dimethylbenzimidazole that occupies one of the axial coordination positions. The opposite coordinate is available for several ligands in bio-medium or in solution; however, known biologically active structures containing adenosyl-or methyl have been considered most often (Figure 1).

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“…The spectral observation of a solvent-exchangeable proton indicates a diminished rate of intermolecular exchange with bulk-H 2 O protons due to protection by H- bonding 6 ). The model of relatively strong H-bonding of OHÀC(2R) is further supported by the observed difference of the exchange-relayed D/H fractionation factors concerning the two exchange-labile ribose functions OHÀC(2R) and OHÀC(5R) of MeCbl (3) [29].…”

Section: 3mentioning

confidence: 99%

“…1), set by the work from the laboratory of Hodgkin [3]. Today still, much of our understanding of the structures and reactivities of vitamin-B 12 derivatives is based on such single-crystal analyses [4 ± 5] that provide precise structural information (even for reactive, paramagnetic Co II derivatives [6]) in the solid state. In the last dozen years, studies by 2D-NMR spectroscopy of solutions of diamagnetic vitamin-B 12 derivatives have begun to complement the X-ray crystallographic work [7 ± 9] and have revealed interesting dynamic aspects of the structures of organometallic vitamin-B 12 derivatives, notably of 2 and of its organometallic moiety [7] [9].…”

mentioning

confidence: 99%