Journal Issue - Volume 16 Issue 1 (January 2007)
From the new Editor
- Brian Matthews
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1002/pro.160001 (p 1-1)
The age of reverse biochemistry
- Steven S. Broyles
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062615307 (p 2-3)
Analysis and prediction of functionally important sites in proteins
- Saikat Chakrabarti, Christopher J. Lanczycki
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062506407 (p 4-13)
Abstract The rapidly increasing volume of sequence and structure information available for proteins poses the daunting task of determining their functional importance. Computational methods can prove to be very useful in understanding and characterizing the biochemical and evolutionary information contained in this wealth of data, particularly at functionally important sites. Therefore, we perform a detailed survey of compositional...
Solution structure of a small protein containing a fluorinated side chain in the core
- Gabriel Cornilescu, Erik B. Hadley, Matthew G. Woll, John L. Markley, Samuel H. Gellman, Claudia C. Cornilescu
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062557707 (p 14-19)
Abstract We report the first high‐resolution structure for a protein containing a fluorinated side chain. Recently we carried out a systematic evaluation of phenylalanine to pentafluorophenylalanine (Phe → F5‐Phe) mutants for the 35‐residue chicken villin headpiece subdomain (c‐VHP), the hydrophobic core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe → F5‐Phe mutations are interesting because...
The effects of cosolutes on protein dynamics: The reversal of denaturant‐induced protein fluctuations by trimethylamine N ‐oxide
- Vicky Doan‐Nguyen, J. Patrick Loria
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062393707 (p 20-29)
Abstract The protein stabilizing effects of the small molecule osmolyte, trimethylamine N‐oxide, against chemical denaturant was investigated by NMR spin‐relaxation measurements and model‐free analysis. In the presence of 0.7 M guanidine hydrochloride increased picosecond‐nanosecond dynamics are observed in the protein ribonuclease A. These increased fluctuations occur throughout the protein, but the most significant increases in flexibility...
Studying multisite binary and ternary protein interactions by global analysis of isothermal titration calorimetry data in SEDPHAT: Application to adaptor protein complexes in cell signaling
- Jon C.D. Houtman, Patrick H. Brown, Brent Bowden, Hiroshi Yamaguchi, Ettore Appella, Lawrence E. Samelson, Peter Schuck
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062558507 (p 30-42)
Abstract Multisite interactions and the formation of ternary or higher‐order protein complexes are ubiquitous features of protein interactions. Cooperativity between different ligands is a hallmark for information transfer, and is frequently critical for the biological function. We describe a new computational platform for the global analysis of isothermal titration calorimetry (ITC) data for the study of binary and ternary...
Efficient molecular docking of NMR structures: Application to HIV‐1 protease
- Sheng‐You Huang, Xiaoqin Zou
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062501507 (p 43-51)
Abstract Docking ligands into an ensemble of NMR conformers is essential to structure‐based drug discovery if only NMR structures are available for the target. However, sequentially docking ligands into each NMR conformer through standard single‐receptor‐structure docking, referred to as sequential docking, is computationally expensive for large‐scale database screening because of the large number of NMR conformers involved....
Contributions of the interdomain loop, amino terminus, and subunit interface to the ligand‐facilitated dimerization of neurophysin: Crystal structures and mutation studies of bovine neurophysin‐I
- Xintian Li, Hunjoong Lee, Jin Wu, Esther Breslow
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062444807 (p 52-68)
Abstract Current evidence indicates that the ligand‐facilitated dimerization of neurophysin is mediated in part by dimerization‐induced changes at the hormone binding site of the unliganded state that increase ligand affinity. To elucidate other contributory factors, we investigated the potential role of neurophysin's short interdomain loop (residues 55–59), particularly the effects of loop residue mutation and of deleting...
A complete algorithm to resolve ambiguity for intersubunit NOE assignment in structure determination of symmetric homo‐oligomers
- Shobha Potluri, Anthony K. Yan, Bruce R. Donald, Chris Bailey‐Kellogg
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062427307 (p 69-81)
Abstract Assignment of nuclear Overhauser effect (NOE) data is a key bottleneck in structure determination by NMR. NOE assignment resolves the ambiguity as to which pair of protons generated the observed NOE peaks, and thus should be restrained in structure determination. In the case of intersubunit NOEs in symmetric homo‐oligomers, the ambiguity includes both the identities of the protons within a subunit, and the identities of the...
Human lysosomal DNase IIα contains two requisite PLD‐signature (HxK) motifs: Evidence for a pseudodimeric structure of the active enzyme species
- Patrick Schäfer, Iwona A. Cymerman, Janusz M. Bujnicki, Gregor Meiss
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062535307 (p 82-91)
Abstract Lysosomal DNase IIα is essential for DNA waste removal and auxiliary apoptotic DNA fragmentation in higher eukaryotes. Despite the key role of this enzyme, little is known about its structure–function relationships. Here, mutational and biochemical analyses were used to characterize human DNase IIα variants expressed in mammalian cells. The resulting data strongly support the hypothesis that the enzyme is a monomeric...
Atomic‐resolution crystal structure of thioredoxin from the acidophilic bacterium Acetobacter aceti
- Courtney M. Starks, Julie A. Francois, Kelly M. MacArthur, Brittney Z. Heard, T. Joseph Kappock
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062519707 (p 92-98)
Abstract The crystal structure of thioredoxin (AaTrx) from the acetic acid bacterium Acetobacter aceti was determined at 1 Å resolution. This is currently the highest resolution crystal structure available for any thioredoxin. Thioredoxins facilitate thiol‐disulfide exchange, a process that is expected to be slow at the low pH values encountered in the A. aceti cytoplasm. Despite the apparent need to function at low pH, neither the active site...
A phosphate‐binding subsite in bovine pancreatic ribonuclease A can be converted into a very efficient catalytic site
- Mohammed Moussaoui, Claudi M. Cuchillo, M. Victòria Nogués
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062251707 (p 99-109)
Abstract A general acid–base catalytic mechanism is responsible for the cleavage of the phosphodiester bonds of the RNA by ribonuclease A (RNase A). The main active site is formed by the amino acid residues His12, His119, and Lys41, and the process follows an endonucleolytic pattern that depends on the existence of a noncatalytic phosphate‐binding subsite adjacent, on the 3′‐side, to the active site; in this region the phosphate...
Direct detection of transient α‐helical states in islet amyloid polypeptide
- Jessica A. Williamson, Andrew D. Miranker
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062486907 (p 110-117)
Abstract The protein islet amyloid polypeptide (IAPP) is a glucose metabolism associated hormone cosecreted with insulin by the β‐cells of the pancreas. In humans with type 2 diabetes, IAPP deposits as amyloid fibers. The assembly intermediates of this process are associated with β‐cell death. Here, we examine the rat IAPP sequence variant under physiological solution conditions. Rat IAPP is mechanistically informative for...
Vaccinia virus N1L protein resembles a B cell lymphoma‐2 (Bcl‐2) family protein
- Mika Aoyagi, Dayong Zhai, Chaofang Jin, Alexander E. Aleshin, Boguslaw Stec, John C. Reed, Robert C. Liddington
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062454707 (p 118-124)
Abstract Poxviruses encode immuno‐modulatory proteins capable of subverting host defenses. The poxvirus vaccinia expresses a small 14‐kDa protein, N1L, that is critical for virulence. We report the crystal structure of N1L, which reveals an unexpected but striking resemblance to host apoptotic regulators of the B cell lymphoma‐2 (Bcl‐2) family. Although N1L lacks detectable Bcl‐2 homology (BH) motifs at the sequence level, we show...
BPPred: A Web‐based computational tool for predicting biophysical parameters of proteins
- Christian D. Geierhaas, Adrian A. Nickson, Kresten Lindorff‐Larsen, Jane Clarke, Michele Vendruscolo
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062383807 (p 125-134)
Abstract We exploit the availability of recent experimental data on a variety of proteins to develop a Web‐based prediction algorithm (BPPred) to calculate several biophysical parameters commonly used to describe the folding process. These parameters include the equilibrium m‐values, the length of proteins, and the changes upon unfolding in the solvent‐accessible surface area, in the heat capacity, and in the radius of gyration. We...




