Abstract
There exists a hierarchical approach to the study of flavoprotein function in biology: investigation in natural systems (by far the most common) (1); using semisynthetic systems, pioneered by Kaiser (2,3), where the flavin is attached near to the active site of a natural enzyme and the flavin chemistry modifies the catalytic behavior of the enzyme; and in fully synthetic systems where the flavin is attached to novel chemical frameworks (4) or synthetic peptides (5–7). The focus of our research falls into the last category, as studies aimed at understanding the molecular basis of catalytic fitness in enzymes are often confounded by the sheer complexity of natural proteins. Using insights drawn from natural systems, we design and synthesize minimalistic structures that assemble the component peptides and prosthetic groups into a functional array. We term these working structures molecular maquettes. The peptide framework of choice is the well-characterized, robust, and structurally defined tetra α-helix bundle, which is a dimer of helix-loop-helix secondary structure motifs, that pack together to form a well defined hydrophobic core (8). To date, there has been much success with this approach, notably the incorporation of heme into tetra α-helix bundle proteins, via bis-histidine axial coordination to the porphyrin iron (9).
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© 1999 Humana Press Inc., Totowa, NJ
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Sharp, R.E., Dutton, P.L. (1999). Flavin Synthesis and Incorporation into Synthetic Peptides. In: Chapman, S.K., Reid, G.A. (eds) Flavoprotein Protocols. Methods in Molecular Biology, vol 131. Humana Press. https://doi.org/10.1385/1-59259-266-X:195
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DOI: https://doi.org/10.1385/1-59259-266-X:195
Publisher Name: Humana Press
Print ISBN: 978-0-89603-734-2
Online ISBN: 978-1-59259-266-1
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