Design of an artificial four-helix bundle metalloprotein via a novel ruthenium(II)-assisted self-assembly process

Ghadiri, Mojtaba; Soares, Christopher; Choi, Chel‐Jong

doi:10.1021/ja00036a072

Cited by 168 publications

(86 citation statements)

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“…The study of proteins, however, is no longer limited to natural proteins. It is now possible to construct proteins that are designed entirely de novo (16)(17)(18)(19)(20). With the ability to design proteins from first principles comes the possibility to design structures by focusing on one type of interaction with the hope that optimizing this type will compensate for the mistakes that may result from an incomplete understanding of other features.…”

Section: Introductionmentioning

confidence: 99%

Periodicity of polar and nonpolar amino acids is the major determinant of secondary structure in self-assembling oligomeric peptides.

Xiong

Buckwalter

Shieh

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

265

171

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The tendency of a polypeptide chain to form ar-helical or ,-strand secondary structure depends upon local and nonlocal effects. Local effects reflect the intrinsic propensities of the amino acid residues for particular secondary structures, while nonlocal effects reflect the positioning of the individual residues in the context of the entire amino acid sequence. In particular, the periodicity of polar and nonpolar residues specifies whether a given sequence is consistent with amphiphilic a-helices or ,8-strands. The importance of intrinsic propensities was compared to that of polar/nonpolar periodicity by a direct competition. Synthetic peptides were designed using residues with intrinsic propensities that favored one or the other type of secondary structure. The polar/nonpolar periodicities of the peptides were designed either to be consistent with the secondary structure favored by the intrinsic propensities of the component residues or in other cases to oppose these intrinsic propensities. Characterization ofthe synthetic peptides demonstrated that in all cases the observed secondary structure correlates with the periodicity of the peptide sequence-even when this secondary structure differs from that predicted from the intrinsic propensities of the component amino acids. The observed secondary structures are concentration dependent, indicating that oligomerization ofthe amphiphilic peptides is responsible for the observed secondary structures. Thus, for selfassembling oligomeric peptides, the polar/nonpolar periodicity can overwhelm the intrinsic propensities of the amino acid residues and serves as the major determinant of peptide secondary structure.The folded structures of proteins are stabilized by a variety of different features, including hydrogen bonding, van der Waals interactions, electrostatic interactions, the hydrophobic effect, and the intrinsic propensities of amino acid side chains for particular secondary structures (1). In recent years, the importance of each of these types of interactions individually has been probed in model peptide systems and in mutagenically altered proteins (2-15). The importance of one type of interaction relative to another type of interaction has received far less attention. This is not surprising since natural proteins typically are stabilized by the concerted action of numerous interrelated features, and it is not possible to isolate any one of these features from all the others. The study of proteins, however, is no longer limited to natural proteins. It is now possible to construct proteins that are designed entirely de novo (16)(17)(18)(19)(20). With the ability to design proteins from first principles comes the possibility to design structures by focusing on one type of interaction with the hope that optimizing this type will compensate for the mistakes that may result from an incomplete understanding of other features. Thus, the emerging field of de novo proteinThe publication costs of this article were defrayed in part by page charge payment. This art...

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Section: Introductionmentioning

confidence: 99%

Periodicity of polar and nonpolar amino acids is the major determinant of secondary structure in self-assembling oligomeric peptides.

Xiong

Buckwalter

Shieh

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

265

171

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“…Thus, the incorporation of metal-binding sites into proteins is a step toward construction of metalloenzymes. To date, however, most metal-binding sites have been incorporated into proteins to impart stability (4), regulate activity (5), aid in purification (6), or mediate their assembly (7). The de novo design of catalytically active metalloproteins has yet to be accomplished as not only metal ligation but also transition state stabilization of the reaction must be considered and will likely remain out of reach for all but the simplest reactions.…”

mentioning

confidence: 99%

Direct selection of antibodies that coordinate metals from semisynthetic combinatorial libraries.

Barbas

Rosenblum

Lerner

1993

Proc. Natl. Acad. Sci. U.S.A.

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An iterative strategy for the selection of catalytic netalloantibodies is described. The first sage of this strategy is validated by the selection ofsemisynthetic antibodies that coordinate a variety of different metal ions and the metal oxide magnetite. These results have implications not only for the development of catalytic m n but also for the development of reagents for magnetic resonance imaging, delivery of radioLsotopes, and purification of recombinant proteins.Metals are important cofactors in enzyme-catalyzed reactions such as phosphoryl and acyl group transfers, aldol condensations, and redox reactions. Indeed, about one-third of nature's enzymes utilize metals in structural or catalytic roles (1). In the realm of organic synthesis, metal-catalyzed reactions are among the only reactions that compete with enzymes in efficiency and ability to control the stereochemical outcome of organic transformations (2, 3). Thus, the incorporation of metal-binding sites into proteins is a step toward construction of metalloenzymes. To date, however, most metal-binding sites have been incorporated into proteins to impart stability (4), regulate activity (5), aid in purification (6), or mediate their assembly (7). The de novo design of catalytically active metalloproteins has yet to be accomplished as not only metal ligation but also transition state stabilization of the reaction must be considered and will likely remain out of reach for all but the simplest reactions.Our interest lies in the de novo creation of catalytic antibodies. To further this goal, we have begun to develop approaches that allow experimenter-controlled evolution of protein architecture (8)(9)(10). These random in vitro methods are particularly applicable to the selection of antibodies that directly coordinate metal cofactors in their combining sites and dffer from our previous approach in which a metal coordination site was designed into an antibody light chain of known structure (11, 12). Here we report the selection of antibodies from semisynthetic combinatorial antibody libraries that ligate metals and metal oxides in their combining sites. MATERIALS ANID METHODS

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“…To a THF solution (30mL) of 2,2'-dithiodianiline (2.5 g, lOmmol) was added pyridine (lOmL) and lauroyl chloride (4.2g, 20mmol) at 0°C and refluxed for 2 h. Removal of solvent gave pale yellow solid. After addition of water, the solid was collected with filtration, washed with successive water, NH 3 aq, water, 2% HClaq, and water. The crude product was dissolved in hot ethanol and left at room temperature to give white crystalline solid, which was collected with filtration, washed with cold ethanol and dried in vacuo over P 2 0 5 .…”

Section: Conhc6 H 4 }Imentioning

confidence: 99%

Molecular Assembly and Micellization of Molybdenum(V, IV) Thiolate and Selenolate Complexes with Long Hydrocarbon Chains

Okamura

Taniuchi

Ueyama

et al. 1999

Polym J

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ABSTRACT:Molybdenum(IV, V) thiolate and selenolate complex with four long bundling hydrocarbon chains connected to the amide group, (Ph4 P)[MovO{S-2-CHiCH2) 10CO NHC6H4 } 4 ] and (NEt4h[Mo 1 vO{Se-2-CHiCH 2 ) 10 CONHC 6 H 4 } 4 ] were synthesized. The four chains are oriented toward the same direction in the solution as established by 1 H NMR. These complexes were soluble in an aqueous micellar solution and stabilized against hydrolysis in such aqueous media efficiently by the hydrocarbon chains. The preliminary results of X-ray analysis revealed the individual molecular assembly behavior which depends significantly on the oxidation state of metal ion and the kind of coordinated atom.KEY WORDS Micellization / Hydrocarbon Chain / Assembly / Molybdenum Complex / From a biological point of view, bundling polypeptides or hydrocarbon chains with the same orientation are interesting models for a protein folding, the active site of enzymes, and molecular recognition in biomembrane.1-4 Previously, we reported molybdenum(V) and molybdenum(IV) complexes containing oriented four acetylamino groups, (NEt 4 )[MovO(S-2-CH 3 CO NHC 6 H 4 ) 4 ] and (NEt 4 )i[Mo 1 vO(S-2-CH 3 CONHC 6 H 4 ) 4 ], whose structure allows unique opportunity to bundle four long hydrocarbon chains on the acetyl groups. 5 Replacement of sulfur by selenium gave isostructual molecule due to their similar chemical properties. The MoOQ 4 (Q = S, Se) core has a potential flexibility depending on the oxidation state of metal ion and a kind of Q which determines distance and character of the Mo-Q bonds. Furthermore some biological activities are considered to be supported in hydrophobic media. To simulate biological hydrophobic environment, ones have used hydrophobic solvents, e.g., chloroform, or aqueous micellar solution where the micelles exclude bulk water and hydrogen bond is supported inside of the hydrophobic micelles. 6 Our complexes with hydrocarbon chains can possess a good affinity to both hydrophobic solvents and micelles.On the other hand, three dimensional construction of molecules or supramolecular structure is one of the most noteworthy problems. Especially, supramolecules involving metal ion have been synthesized for their unique physical properties. An ordered orientation of layered molecules in the solid state leads to interesting electronic and magnetic properties. 7 -9 Many of the known such supramolecules exist as assemblies of molecules having two dimensional spread and/or long linear hydrocarbon chains perpendicular to a disk-shape molecule, e.g., porphyrin. 1 o-i 3 Some molecules having bent structure 14 or radial chains 15 have also been reported. Although many kinds of molecules have been known, these molecules have a rigid structure connecting hydrocarbon chains. We have tried to design novel molecules containing flexible basic structure for developing a new t To whom correspondence should be addressed. type of supramolecule.In this paper, the structures of molybdenum(V, IV) complexes containing long hydrocarbon chains with speci...

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Design of an artificial four-helix bundle metalloprotein via a novel ruthenium(II)-assisted self-assembly process

Cited by 168 publications

References 1 publication

Periodicity of polar and nonpolar amino acids is the major determinant of secondary structure in self-assembling oligomeric peptides.

Periodicity of polar and nonpolar amino acids is the major determinant of secondary structure in self-assembling oligomeric peptides.

Direct selection of antibodies that coordinate metals from semisynthetic combinatorial libraries.

Molecular Assembly and Micellization of Molybdenum(V, IV) Thiolate and Selenolate Complexes with Long Hydrocarbon Chains

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