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On the Importance of Ribose Orientation in the Substrate Activation of the Coenzyme B 12 ‐Dependent Mutases
Author(s) -
Durbeej Bo,
Sandala Gregory M.,
Bucher Denis,
Smith David M.,
Radom Leo
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200901002
Subject(s) - corrin , ribose , chemistry , ring (chemistry) , moiety , stereochemistry , substrate (aquarium) , cofactor , crystallography , enzyme , biology , biochemistry , ecology , organic chemistry
Abstract The degree to which the corrin ring portion of coenzyme B 12 can facilitate the H‐atom‐abstraction step in the glutamate mutase (GM)‐catalyzed reaction of ( S )‐glutamate has been investigated with density functional theory. The crystal structure of GM identifies two possible orientations of the ribose portion of coenzyme B 12 . In one orientation (A), the OH groups of the ribose extend away from the corrin ring, whereas in the other orientation (B) the OH groups, especially that involving O3′, are instead directed towards the corrin ring. Our calculations identify a sizable stabilization amounting to about 30 kJ mol −1 in the transition structure (TS) complex corresponding to orientation B (TS B CorIm). In the TS complex where the ribose instead is positioned in orientation A, no such effect is manifested. The observed stabilization in TS B CorIm appears to be the result of favorable interactions involving O3′ and the corrin ring, including a CH⋅⋅⋅O hydrogen bond. We find that the degree of stabilization is not particularly sensitive to the CoC distance. Our calculations show that any potential stabilization afforded to the H‐atom‐abstraction step by coenzyme B 12 is sensitive to the orientation of the ribose moiety.