Coenzyme binding site crystallographic studies

II) complexes inhibit pig heart m-MDH at low metal concentrations (1-4 moles of ions per mole of enzyme) ( ). Similar platinum compounds inhibit pig heart s-MDH (91). In the case of s-MDH, the inhibition is essentially irreversible but the rate of inhibition is reduced in the presence of coenzyme (91). The steric relationships of these metal binding sites relative to the coenzyme binding sites were determined by X-ray crystallographic studies (91). Phenols and substituted phenols are inhibitors of pig heart m-MDH and appear to be competitive with NAD+ (98). 

Crystallographic studies at 2.5 A resolution have been carried out on the enzyme from E.coli [67] (Fig. 15) and Lactobacillus casei [68,69] (Fig. 16). Residue numbers in what follows refer to the L. casei enzyme sequence [70]. The binding sites for the substrate and coenzyme are not located in separate domains, but are composed of overlapping portions involving mainly the N-terminal two-thirds of the polypeptide... 

Crystallographic studies with GM from Cl. cochlearium have provided a detailed structural picture of the enzyme, in which the corrinoid cofactor is bound base-off/His-on again and at the interface between the subunits a and The cobalt-coordinating histidine is part of an H-bonded regulatory His-Asp-Ser triad. Detailed analysis of GM with the bound coenzyme B12 (3) revealed the position of the ribose part of the 5 -deoxyadenosyl moiety to be disordered and to be present in two conformations, related to each other by a pseudo-rotation of the furanose ring. One of these structures places the 5 -methylene group of the adenosine close to the position of the corrin-bound cobalt center, but at a distance of about 3.1 A, and thus appears to have features expected for the direct product of the homolysis of the Co-C bond of the bound cofactor (3). In the other conformation, the 5 methylene carbon is at a distance of about 4.5 A from the metal center and is displaced toward the substrate-binding site, as if in van der Waals contact with the bound substrate. In this way, GM... 

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