Structural and enzymatic studies of a new analogue of coenzyme B12 with an alpha-adenosyl upper axial ligand

Biochemistry
Kenneth L BrownH M Marques

Abstract

A new analogue of coenzyme B12 (5'-deoxyadenosylcobalamin, AdoCbl), in which the configuration of the N-glycosidic bond in the Ado ligand is inverted [(alpha-ribo)AdoCbl], has been synthesized and its crystal structure determined by X-ray diffraction [MoKalpha, lambda = 0.71073 A, monoclinic P212121, a = 16.132(12) A, b = 21. 684(15) A, c = 27.30(3) A, 9611 independent reflections, R1 = 0. 0708]. As suggested by molecular mechanics modeling before the structure was known, the Ado ligand lies over the southern quadrant of the molecule, as is the case for AdoCbl. The most striking feature of the structure is disorder in the orientation of the adenine (Ade) moiety relative to the ribose of the Ado ligand. This was resolved with a two-state model in which in the major (0.57 occupancy) conformer the A16(O)-A11-A9(N)-A8 dihedral angle is 1.9 degrees and the Ade is virtually perpendicular to the corrin ring; in the minor conformer, the Ade is tilted down, and this dihedral is -48.7 degrees. The Co-C and axial Co-N bond lengths and the Co-C-C bond angle are quite similar to those in AdoCbl. The corrin ring is considerably flatter than that of AdoCbl, with a fold angle of 11.7 degrees. The molecule was successfully modeled by molecular ...Continue Reading

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Citations

Jan 23, 1999·Current Opinion in Chemical Biology·P K Mishra, D G Drueckhammer
Dec 13, 2006·Nucleosides, Nucleotides & Nucleic Acids·Tilak Chandra, Kenneth L Brown
Jan 6, 2009·Tetrahedron·Tilak Chandra, Kenneth L Brown
Oct 20, 2012·Chemistry : a European Journal·Peter FriedrichBernard T Golding
Jan 6, 2009·Dalton Transactions : an International Journal of Inorganic Chemistry·Hanaa A HassaninNicola E Brasch
Nov 21, 2014·Biochemistry·Terence S CroftsMichiko E Taga
Apr 21, 2021·Dalton Transactions : an International Journal of Inorganic Chemistry·Mads Sondrup MøllerChristine J McKenzie
Jun 17, 2006·The Journal of Organic Chemistry·Tilak ChandraKenneth L Brown

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