2002
DOI: 10.1021/bi026104z
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Substrate-Induced Conformational Change of a Coenzyme B12-Dependent Enzyme:  Crystal Structure of the Substrate-Free Form of Diol Dehydratase,

Abstract: Substrate binding triggers catalytic radical formation through the cobalt-carbon bond homolysis in coenzyme B12-dependent enzymes. We have determined the crystal structure of the substrate-free form of Klebsiella oxytoca diol dehydratase*cyanocobalamin complex at 1.85 A resolution. The structure contains two units of the heterotrimer consisting of alpha, beta, and gamma subunits. As compared with the structure of its substrate-bound form, the beta subunits are tilted by approximately 3 degrees and cobalamin is… Show more

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Cited by 64 publications
(70 citation statements)
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“…Recent crystallographic studies for two B 12 -containg enzymes, glutamate mutase (GLM) 48 and diol dehydratase (DDH), 49 suggest that the main contribution to Co-C bond cleavage is substrate-induced deformation of the coenzyme, although the evidence is complicated by the likelihood that the Co(III) is reduced to Co(II) in the crystals. Recent QM/MM calculations reported by Jensen and Ryde 50 likewise support adenosyl deformation as the most feasible mechanism of Co-C activation.…”
Section: Implications For Protein Activation Of B 12 Coenzymesmentioning
confidence: 99%
“…Recent crystallographic studies for two B 12 -containg enzymes, glutamate mutase (GLM) 48 and diol dehydratase (DDH), 49 suggest that the main contribution to Co-C bond cleavage is substrate-induced deformation of the coenzyme, although the evidence is complicated by the likelihood that the Co(III) is reduced to Co(II) in the crystals. Recent QM/MM calculations reported by Jensen and Ryde 50 likewise support adenosyl deformation as the most feasible mechanism of Co-C activation.…”
Section: Implications For Protein Activation Of B 12 Coenzymesmentioning
confidence: 99%
“…Substrate Switch-The structures of two AdoCbl-dependent enzymes, methylmalonyl-CoA mutase and diol dehydratase, reveal that substrate binding causes significant conformational changes at the overall fold level (50,51). The bound substrate pushes Gln␣ 336 and Phe␣ 374 toward pyrrole rings A and D of the corrin ring in diol dehydratase.…”
mentioning
confidence: 99%
“…As a result, this enzyme displays movement of cobalamin and the ␤-subunit with respect to the ␣-subunit upon substrate binding, which causes the tilting of cobalamin. This is considered responsible for the substrate switch or substrate-induced additional labilization of the Co-C bond (51). To test this possibility, the structure of the substrate-free form of EAL was also analyzed.…”
mentioning
confidence: 99%
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“…The addition from 5 mg/l to 20 mg/l of vitamin B12, production was negatively impacted because of its interaction with glycerol. An irreversible binding of the vitamin B12 and glycerol with the enzyme, forms alkylcobalamines, and to avoid low activity of the enzyme, the amount of glycerol should be controlled [20,[29][30][31][32], but also the amount of vitamin should be controlled. As a consequence of the normal catalytic cycle with glycerol, the coenzyme B12 is occasionally rendered inactive (B12-inact).…”
Section: Box Hunter and Hunter Full Fatorial Doementioning
confidence: 99%