Category: publications

X-ray structure of native scorpion toxin BmBKTx1 by racemic protein crystallography using direct methods

Mandal K, Pentelute BL, Tereshko V, Kossiakoff AA, Kent SB

J. Am. Chem. Soc. 2009 Feb;131(4):1362-3

PMID: 19133782

Abstract

Racemic protein crystallography, enabled by total chemical synthesis, has allowed us to determine the X-ray structure of native scorpion toxin BmBKTx1; direct methods were used for phase determination. This is the first example of a protein …

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Principal determinants leading to transition state formation of a protein-protein complex, orientation trumps side-chain interactions

Horn JR, Sosnick TR, Kossiakoff AA

Proc. Natl. Acad. Sci. U.S.A. 2009 Feb;106(8):2559-64

PMID: 19196954

Abstract

The binding transition state (TS) is the rate-limiting step for transient molecular interactions. This important step in the molecular recognition process, however, is largely understood only at a qualitative level. To establish a more quantitative picture of the TS …

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Understanding mechanisms governing protein-protein interactions from synthetic binding interfaces

Kossiakoff AA, Koide S

Curr. Opin. Struct. Biol. 2008 Aug;18(4):499-506

PMID: 18638552

Abstract

Recent advances in methodologies and design of combinatorial library selection have enabled comprehensive characterization of sequence space for protein-protein interaction interfaces and generation of fully synthetic binding interfaces. By exhaustively introducing and quantitatively analyzing mutations in natural interfaces, new insights into their …

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Toward chaperone-assisted crystallography: protein engineering enhancement of crystal packing and X-ray phasing capabilities of a camelid single-domain antibody (VHH) scaffold

Tereshko V, Uysal S, Koide A, Margalef K, Koide S, Kossiakoff AA

Protein Sci. 2008 Jul;17(7):1175-87

PMID: 18445622

Abstract

A crystallization chaperone is an auxiliary protein that binds to a target of interest, enhances and modulates crystal packing, and provides high-quality phasing information. We critically evaluated the effectiveness of a camelid single-domain antibody (V(H)H) as …

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X-ray structure of snow flea antifreeze protein determined by racemic crystallization of synthetic protein enantiomers

Pentelute BL, Gates ZP, Tereshko V, Dashnau JL, Vanderkooi JM, Kossiakoff AA, Kent SB

J. Am. Chem. Soc. 2008 Jul;130(30):9695-701

PMID: 18598029

Abstract

Chemical protein synthesis and racemic protein crystallization were used to determine the X-ray structure of the snow flea antifreeze protein (sfAFP). Crystal formation from a racemic solution containing equal amounts of the …

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The 1.38 A crystal structure of DmsD protein from Salmonella typhimurium, a proofreading chaperone on the Tat pathway

Qiu Y, Zhang R, Binkowski TA, Tereshko V, Joachimiak A, Kossiakoff A

Proteins 2008 May;71(2):525-33

PMID: 18175314

Abstract

The DmsD protein is necessary for the biogenesis of dimethyl sulphoxide (DMSO) reductase in many prokaryotes. It performs a critical chaperone function initiated through its binding to the twin-arginine signal peptide of DmsA, the catalytic subunit of …

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Synthetic antibodies for specific recognition and crystallization of structured RNA

Ye JD, Tereshko V, Frederiksen JK, Koide A, Fellouse FA, Sidhu SS, Koide S, Kossiakoff AA, Piccirilli JA

Proc. Natl. Acad. Sci. U.S.A. 2008 Jan;105(1):82-7

PMID: 18162543

Abstract

Antibodies that bind protein antigens are indispensable in biochemical research and modern medicine. However, knowledge of RNA-binding antibodies and their application in the ever-growing RNA field is …

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High-throughput generation of synthetic antibodies from highly functional minimalist phage-displayed libraries

Fellouse FA, Esaki K, Birtalan S, Raptis D, Cancasci VJ, Koide A, Jhurani P, Vasser M, Wiesmann C, Kossiakoff AA, Koide S, Sidhu SS

J. Mol. Biol. 2007 Nov;373(4):924-40

PMID: 17825836

Abstract

We have previously established a minimalist approach to antibody engineering by using a phage-displayed framework to support complementarity determining region (CDR) diversity restricted …

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Exploring the capacity of minimalist protein interfaces: interface energetics and affinity maturation to picomolar KD of a single-domain antibody with a flat paratope

Koide A, Tereshko V, Uysal S, Margalef K, Kossiakoff AA, Koide S

J. Mol. Biol. 2007 Nov;373(4):941-53

PMID: 17888451

Abstract

A major architectural class in engineered binding proteins (“antibody mimics”) involves the presentation of recognition loops off a single-domain scaffold. This class of binding proteins, both natural and synthetic, has a strong tendency to bind …

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Exploring and designing protein function with restricted diversity

Sidhu SS, Kossiakoff AA

Curr Opin Chem Biol 2007 Jun;11(3):347-54

PMID: 17500026

Abstract

Combinatorial libraries with restricted diversity can be used to rapidly map binding energetics across protein interfaces. Shotgun scanning strategies have been used for alanine scanning and for alternative mutagenesis schemes that provide high-resolution functional views of binding interfaces. In addition, synthetic antibodies …

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