β‐Hairpin Peptides: Heme Binding, Catalysis, and Structure in Detergent Micelles

Mahajan, Mukesh; Bhattacharjya, Surajit

doi:10.1002/anie.201300241

Cited by 31 publications

(31 citation statements)

References 59 publications

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“…In another functional aspect using aromatic interactions, Mahajan and Bhattacharjya reported a de novo design of membrane active β‐hairpin and α‐helical scaffolds stabilized by aromatic interactions . Tryptophan and histidine residues were also utilized to anchor the scaffold into lipid micelles and bind heme.…”

Section: Future Prospectsmentioning

confidence: 99%

Implications of aromatic–aromatic interactions: From protein structures to peptide models

2015

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With increasing structural information on proteins, the opportunity to understand physical forces governing protein folding is also expanding. One of the significant non-covalent forces between the protein side chains is aromatic-aromatic interactions. Aromatic interactions have been widely exploited and thoroughly investigated in the context of folding, stability, molecular recognition, and self-assembly processes. Through this review, we discuss the contribution of aromatic interactions to the activity and stability of thermophilic, mesophilic, and psychrophilic proteins. Being hydrophobic, aromatic amino acids tend to reside in the protein hydrophobic interior or transmembrane segments of proteins. In such positions, it can play a diverse role in soluble and membrane proteins, and in a-helix and b-sheet stabilization. We also highlight here some excellent investigations made using peptide models and several approaches involving arylaryl interactions, as an increasingly popular strategy in protein and peptide engineering. A recent survey described the existence of aromatic clusters (trimer, tetramer, pentamer, and higher order assemblies), revealing the self-associating property of aryl groups, even in folded protein structures. The application of this self-assembly of aromatics in the generation of modern bionanomaterials is also discussed.

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Section: Future Prospectsmentioning

confidence: 99%

Implications of aromatic–aromatic interactions: From protein structures to peptide models

2015

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“…Notably, d -Pro adjacent to a β-branched amino acid is suggestive of a type II′ β-turn, 15 an oft-studied motif in a number of peptide-based catalysts from our lab 16 and others. 17 To examine the existence of this structural element within 1 , we resorted to the examination of further altered sequences within on-bead peptide libraries.…”

Section: Resultsmentioning

confidence: 99%

Experimental Lineage and Functional Analysis of a Remotely Directed Peptide Epoxidation Catalyst

Lichtor

Miller

2014

J. Am. Chem. Soc.

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We describe mechanistic investigations of a catalyst (1) that leads to selective epoxidation of farnesol at the 6,7-position, remote from the hydroxyl directing group. The experimental lineage of peptide 1 and a number of resin-bound peptide analogues were examined to reveal the importance of four N-terminal residues. We examined the selectivity of truncated analogues to find that a trimer is sufficient to furnish the remote selectivity. Both 1D and 2D 1H NMR studies were used to determine possible catalyst conformations, culminating in proposed models showing possible interactions of farnesol with a protected Thr side chain and backbone NH. The models were used to rationalize the selectivity of a modified catalyst (17) for the 6,7-position relative to an ether moiety in two related substrates.

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“…[19][20][21][22] The designing of functional membrane proteins containing single heme units, either in helical TM systems or more recently in b-hairpins, has been reported. [23][24][25][26][27][28] To achieve electron transfer across the membrane, it is necessary to develop TM protein systems that can accommodate closely placed redoxactive cofactors (or multiple porphyrins) to channel electrons across the bilayer. To this end, Korendovych et al have recently described the design of a TM sequence, termed PRIME, that folds into a tetramer upon binding to two molecules of a nonnatural iron diphenylporphyrin.…”

mentioning

confidence: 99%

Designed Di‐Heme Binding Helical Transmembrane Protein

Mahajan

Bhattacharjya

2014

ChemBioChem

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De novo designing of functional membrane proteins is fundamental in terms of understanding the structure, folding, and stability of membrane proteins. In this work, we report the design and characterization of a transmembrane protein, termed HETPRO (HEme-binding Transmembrane PROtein), that binds two molecules of heme in a membrane and catalyzes oxidation/reduction reactions. The primary structure of HETPRO has been optimized in a guided fashion, from an antimicrobial peptide, for transmembrane orientation, defined 3D structure, and functions. HETPRO assembles into a tetrameric form, from an apo dimeric helical structure, in complex with cofactor in detergent micelles. The NMR structure of the apo HETPRO in micelles reveals an antiparallel helical dimer that inserts into the nonpolar core of detergent micelles. The well-defined structure of HETPRO and its ability to bind to heme moieties could be utilized to develop a functional membrane protein mimic for electron transport and photosystems.

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β‐Hairpin Peptides: Heme Binding, Catalysis, and Structure in Detergent Micelles

Cited by 31 publications

References 59 publications

Implications of aromatic–aromatic interactions: From protein structures to peptide models

Implications of aromatic–aromatic interactions: From protein structures to peptide models

Experimental Lineage and Functional Analysis of a Remotely Directed Peptide Epoxidation Catalyst

Designed Di‐Heme Binding Helical Transmembrane Protein

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