Journal Issue - Volume 15 Issue 5 (May 2006)
The contribution of the residues from the main hydrophobic core of ribonuclease A to its pressure‐folding transition state
- Josep Font, Antoni Benito, Reinhard Lange, Marc Ribó, Maria Vilanova
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.052050306 (p 1000-1009)
Abstract The role of hydrophobic interactions established by the residues that belong to the main hydrophobic core of ribonuclease A in its pressure‐folding transition state was investigated using the Φ‐value method. The folding kinetics was studied using pressure‐jump techniques both in the pressurization and depressurization directions. The ratio between the folding activation volume and the reaction volume (βp‐value), which is an...
Solution structure of the antifreeze‐like domain of human sialic acid synthase
- Toshiyuki Hamada, Yoko Ito, Takamasa Abe, Fumiaki Hayashi, Peter Güntert, Makoto Inoue, Takanori Kigawa, Takaho Terada, Mikako Shirouzu, Mayumi Yoshida, Akiko Tanaka, Sumio Sugano, Shigeyuki Yokoyama, Hiroshi Hirota
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051700406 (p 1010-1016)
Abstract The structure of the C‐terminal antifreeze‐like (AFL) domain of human sialic acid synthase was determined by NMR spectroscopy. The structure comprises one α‐ and two single‐turn 310‐helices and two β‐strands, and is similar to those of the type III antifreeze proteins. Evolutionary trace analyses of the type III antifreeze protein family suggested that the class‐specific residues in the human and bacterial AFL domains are important ...
An algorithm for predicting protein–protein interaction sites: Abnormally exposed amino acid residues and secondary structure elements
- Jemima Hoskins, Simon Lovell, Tom L. Blundell
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051589106 (p 1017-1029)
Abstract Multiprotein systems mediate most regulatory processes in living organisms. Although the structures of the individual proteins are often defined, less is known of the structures of multiprotein systems. Computational methods for predicting interfaces, using evolutionary conservation and/or physicochemical data, have been developed. Here we consider the use of solvent accessibility, residue propensity, and hydrophobicity, in...
Solution structure of Asl1650, an acyl carrier protein from Anabaena sp. PCC 7120 with a variant phosphopantetheinylation‐site sequence
- Margaret A. Johnson, Wolfgang Peti, Torsten Herrmann, Ian A. Wilson, Kurt Wüthrich
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051964606 (p 1030-1041)
Abstract Cyanobacteria, such as Anabaena, produce a variety of bioactive natural products via polyketide synthases (PKS), nonribosomal peptide synthetases (NRPS), and hybrid peptide/polyketide pathways. The protein Asl1650, which is a member of the acyl carrier protein family from the cyanobacterium Anabaena sp. PCC 7120, is encoded in a region of the Anabaena genome that is rich in PKS and NRPS genes. To gain new insight into the physiological...
The C‐terminal domain of the transcriptional corepressor CtBP is intrinsically unstructured
- Marco Nardini, Dmitri Svergun, Peter V. Konarev, Stefania Spanò, Mauro Fasano, Chiara Bracco, Alessandra Pesce, Alessandra Donadini, Claudia Cericola, Francesco Secundo, Alberto Luini, Daniela Corda, Martino Bolognesi
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062115406 (p 1042-1050)
Abstract C‐terminal binding proteins (CtBPs) are moonlighting proteins involved in nuclear transcriptional corepression and in Golgi membrane tubule fission. Structural information on CtBPs is available for their substrate‐binding domain, responsible for transcriptional repressor recognition/binding, and for the nucleotide‐binding domain, involved in NAD(H)‐binding and dimerization. On the contrary, little is known about the...
Src kinase activation: A switched electrostatic network
- Elif Ozkirimli, Carol Beth Post
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051999206 (p 1051-1062)
Abstract Src tyrosine kinases are essential in numerous cell signaling pathways, and improper functioning of these enzymes has been implicated in many diseases. The activity of Src kinases is regulated by conformational activation, which involves several structural changes within the catalytic domain (CD): the orientation of two lobes of CD; rearrangement of the activation loop (A‐loop); and movement of an α‐helix (αC), which is...
Modulation of protein aggregation by polyethylene glycol conjugation: GCSF as a case study
- Rahul S. Rajan, Tiansheng Li, Mohini Aras, Christopher Sloey, Weston Sutherland, Hiromi Arai, Robert Briddell, Olaf Kinstler, Alexis M.K. Lueras, Yu Zhang, Heather Yeghnazar, Michael Treuheit, David N. Brems
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.052004006 (p 1063-1075)
Abstract Polyethylene glycol (PEG) conjugation to proteins has emerged as an important technology to produce drug molecules with sustained duration in the body. However, the implications of PEG conjugation to protein aggregation have not been well understood. In this study, conducted under physiological pH and temperature, N‐terminal attachment of a 20 kDa PEG moiety to GCSF had the ability to (1) prevent protein precipitation by...
Modular organization of FDH: Exploring the basis of hydrolase catalysis
- Steven N. Reuland, Alexander P. Vlasov, Sergey A. Krupenko
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.052062806 (p 1076-1084)
Abstract An abundant enzyme of liver cytosol, 10‐formyltetrahydrofolate dehydrogenase (FDH), is an interesting example of a multidomain protein. It consists of two functionally unrelated domains, an aldehyde dehydrogenase‐homologous domain and a folate‐binding hydrolase domain, which are connected by an ∼100‐residue linker. The amino‐terminal hydrolase domain of FDH (Nt‐FDH) is a homolog of formyl transferase enzymes that utilize 10‐formyl‐THF...
Sequential reorganization of β‐sheet topology by insertion of a single strand
- Martin Sagermann, Walter A. Baase, Brian W. Matthews
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.052018006 (p 1085-1092)
Abstract Insertions, duplications, and deletions of sequence segments are thought to be major evolutionary mechanisms that increase the structural and functional diversity of proteins. Alternative splicing, for example, is an intracellular editing mechanism that is thought to generate isoforms for 30%–50% of all human genes. Whereas the inserted sequences usually display only minor structural rearrangements at the insertion site,...
Calorimetric and structural studies of the nitric oxide carrier S‐nitrosoglutathione bound to human glutathione transferase P1‐1
- Ramiro Téllez‐Sanz, Eleonora Cesareo, Marzia Nuccetelli, Ana M. Aguilera, Carmen Barón, Lorien J. Parker, Julian J. Adams, Craig J. Morton, Mario Lo Bello, Michael W. Parker, Luis García‐Fuentes
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.052055206 (p 1093-1105)
Abstract The nitric oxide molecule (NO) is involved in many important physiological processes and seems to be stabilized by reduced thiol species, such as S‐nitrosoglutathione (GSNO). GSNO binds strongly to glutathione transferases, a major superfamily of detoxifying enzymes. We have determined the crystal structure of GSNO bound to dimeric human glutathione transferase P1‐1 (hGSTP1‐1) at 1.4 Å resolution. The GSNO ligand binds in...
Tunnel plasticity and quaternary structural integrity of a pentameric protein ring
- Kenneth J. Woycechowsky, Florian P. Seebeck, Donald Hilvert
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.052044606 (p 1106-1114)
Abstract Cyclic protein oligomers are common in cells. However, the importance of the residues that line the central tunnel of protein rings for overall architectural integrity is not well understood. To investigate the role of tunnel positions in protein assembly and stability, we prepared variants of the homo‐pentameric lumazine synthase (LS) from Saccharomyces cerevisiae in which the three residues that line the middle of the tunnel were...
Enhancing functional production of G protein‐coupled receptors in Pichia pastoris to levels required for structural studies via a single expression screen
- Nicolas André, Nadia Cherouati, Cécile Prual, Tania Steffan, Gabrielle Zeder‐Lutz, Thierry Magnin, Franc Pattus, Hartmut Michel, Renaud Wagner, Christoph Reinhart
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062098206 (p 1115-1126)
Abstract We have optimized the expression level of 20 mammalian G protein‐coupled receptors (GPCRs) in the methylotrophic yeast Pichia pastoris. We found that altering expression parameters, including growth temperature, and supplementation of the culture medium with specific GPCR ligands, histidine, and DMSO increased the amount of functional receptor, as assessed by ligand binding, by more than eightfold over standard expression conditions....
Secondary structure, orientation, and oligomerization of phospholemman, a cardiac transmembrane protein
- Andrew J. Beevers, Andreas Kukol
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051899406 (p 1127-1132)
Abstract Human phospholemman (PLM) is a 72‐residue protein, which is expressed at high density in the cardiac plasma membrane and in various other tissues. It forms ion channels selective for K+, Cl−, and taurine in lipid bilayers and colocalizes with the Na+/K+‐ATPase and the Na+/Ca2+‐exchanger, which may suggest a role in the regulation of cell volume. Here we present the first structural data based on synthetic peptides representing the...
Inhibition of insulin fibrillogenesis with targeted peptides
- Todd J. Gibson, Regina M. Murphy
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051879606 (p 1133-1141)
Abstract Under conditions of acidic pH and elevated temperature, insulin partially unfolds and aggregates into highly structured amyloid fibrils. Aggregation of insulin leads to loss of activity and can trigger an unwanted immune response. Compounds that prevent protein aggregation have been used to stabilize insulin; these compounds generally suppress aggregation only at relatively high inhibitor concentrations. For example,...
Structure and dynamics of the epidermal growth factor receptor C‐terminal phosphorylation domain
- Nam Y. Lee, Theodore L. Hazlett, John G. Koland
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.052045306 (p 1142-1152)
Abstract The C‐terminal phosphorylation domain of the epidermal growth factor receptor is believed to regulate protein kinase activity as well as mediate the assembly of signal transduction complexes. The structure and dynamics of this proposed autoregulatory domain were examined by labeling the extreme C terminus of the EGFR intracellular domain (ICD) with an extrinsic fluorophore. Fluorescence anisotropy decay analysis of the...




