Albaflavenone monooxygenase, Streptomyces coelicolor A3(2)

Albaflavenone monooxygenase (CYP170A1) (EC from Streptomyces coelicolor A3(2) catalyzes the last two steps in the biosynthesis of the antibiotic albaflavenone (Function 1) [32]. Study of the crystal structure of albaflavenone monooxygenase showed that it exists as a dimer having two chains, each consisting of a single, a orthogonal bundle (Fig. 2.4). These studies also revealed a second,

Albaflavenone monooxygenase

Figure 2.4 Albaflavenone monooxygenase. The monooxygenase and terpene synthase active sites are shown in blue and red respectively in the (a) cartoon and (b) surface representation of Albaflavenone monooxygenase (PDB: 3EL3). (See color plate section for the color representation of this figure.)

completely distinct, catalytic activity of a terpene synthase (EC [33] which is involved in the synthesis of farnesene isomers from farnesyl diphosphate (Function 2), by identification of signature sequences and motifs associated with terpene synthases. The residues Trp92, Pro274, Val338, Ile447, and Thr448 are involved in the monooxygenase activity, whereas the residues Arg116, Leu244, Leu248, Glu263, Val268, Leu271, Ile 272, and Phe-415 are associated with the terpene synthase activity which are located in different pockets in the protein. The monooxygenase activity was found to be optimal over the pH range 7.2-8 and was found to decline at lower pH values which favor terpene synthase activity (pH 5.5-6.5). This suggests that the two different enzymatic states of the protein possess optimal conformations at distinct pHs.

MAPK1/ERK2, Homo sapiens

Studies to characterize the human protein-DNA interactome revealed the human mitogen-activated protein kinase 1 (MAPK1) or extracellular signal-r kinase 2 (ERK2) (Function 1) as a DNA-binding transcriptional repressor (Function 2) that regulates interferon gamma signaling [34]. The crystal structure of the human MAPK1 exists as a monomer which contains two domains: a discontinuous оф 2- layer sandwich domain and a mainly a-orthogonal bundle domain (Fig. 2.5). The kinase active site residues involve Asp147, Lys149, Ser151, and Asn152. The motif that has been found to help in binding DNA are 259 K ARN Y LLSLP H K N K V P W N R277. It can be seen from Figure 2.5 that the kinase active site is located far from the DNA-binding motif.

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