Cofactor binding

Miley, M.J., Zielinska, A.K., Keenan, J.E., Bratton, S.M., Pandya, A.R. andRedinbol, M.R. (2007) Crystal structure of the cofactor-binding domain of the human phase II drug-metabolism enzyme UDP-glucuronosyltransferase 2B7. Journal of Molecular Biology,... 

Whenever a TrEMBL entry is recognized by these procedures as a true member of a certain protein family, annotation about the potential function, active sites, cofactors, binding sites, domains, and subcellular locations is added to the entry. The main source of the annotation is compiled by extracting the annotation that is common to all SWISS-... 

Two-dimensional heteronuclear ( H- N) nuclear magnetic relaxation studies indicate that the dihydrofolate reductase-folate complex exhibits a diverse range of backbone fluctuations on the time-scale of picoseconds to nanoseconds To assess whether these dynamical features influence Michaelis complex formation, Miller et al used mutagenesis and kinetic measurements to assess the role of a strictly conserved residue, namely Gly-121, which displays large-amplitude backbone motions on the nanosecond time scale. Deletion of Gly-121 dramatically reduces the hydride transfer rate by 550 times there is also a 20-times decrease in NADPH cofactor binding affinity and a 7-fold decrease for NADP+ relative to wild-type. Insertion mutations significantly decreased both... 

The C-terminal portion of the NOS protein closely resembles to cytochrome P-450 reductase, possesses many of the same cofactor binding sites, and basically performs the same functions. Consequently, this portion is often referred to as the reductase domain. At the extreme C-terminus is an NADPH binding region, which is conserved in all NOS and aligns perfectly with that of cytochrome P-450 reductase. The NADPH binding site is followed, in turn, by flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) consensus sequences. 

Wootton, J.C., Nicolson, R.E., Cock, J.M., Walters, D.E., Burke, J.F., Doyle, W.A. Bray, R.C. (1991). Enzymes depending on the pterin molybdenum cofactor sequence families, spectroscopic properties of molybdenum and possible cofactor-binding domains. Bio-chimica et Biophysica Acta 1057, 157-85. 

Figure 10.6 Crystal structure of parts of the cofactor binding pocket of the (R)-alcohol dehydrogenase from L brevis.

The reversibility of the cofactor binding by PDC was demonstrated in 1941 by Green and co-workers [33] and by Kubowitz and Liittgens [69] (Scheme 4). Schellenberger confirmed these results in 1967 and postulated a first mechanisti-cal model [40]. 

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