Journal Issue - Volume 15 Issue 2 (February 2006)
Prevention of amyloid fibril formation of amyloidogenic chicken cystatin by site‐specific glycosylation in yeast
- Jianwei He, Youtao Song, Nobuhiro Ueyama, Akira Saito, Hiroyuki Azakami, Akio Kato
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051753306 (p 213-222)
Abstract To address the role of glycosylation on fibrillogenicity of amyloidogenic chicken cystatin, the consensus sequence for N‐linked glycosylation (Asn106‐Ile108 → Asn106‐Thr108) was introduced by site‐directed mutagenesis into the wild‐type and amyloidogenic chicken cystatins to construct the glycosylated form of chicken cystatins. Both the glycosylated and unglycosylated forms of wild‐type and amyloidogenic mutant I66Q cystatin were...
The allosteric transition in DnaK probed by infrared difference spectroscopy. Concerted ATP‐induced rearrangement of the substrate binding domain
- Fernando Moro, Vanesa Fernández‐Sáiz, Arturo Muga
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051732706 (p 223-233)
Abstract The biological activity of DnaK, the bacterial representative of the Hsp70 protein family, is regulated by the allosteric interaction between its nucleotide and peptide substrate binding domains. Despite the importance of the nucleotide‐induced cycling of DnaK between substrate‐accepting and releasing states, the heterotropic allosteric mechanism remains as yet undefined. To further characterize this mechanism, the...
The redox couple of the cytochrome c
- Abel Schejter, Michael D. Ryan, Erica R. Blizzard, Chongyao Zhang, Emanuel Margoliash, Benjamin A. Feinberg
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051825906 (p 234-241)
Abstract Contrary to most heme proteins, ferrous cytochrome c does not bind ligands such as cyanide and CO. In order to quantify this observation, the redox potential of the ferric/ferrous cytochrome c–cyanide redox couple was determined for the first time by cyclic voltammetry. Its E0′ was −240 mV versus SHE, equivalent to −23.2 kJ/mol. The entropy of reaction for the reduction of the cyanide complex was also determined. From a thermodynamic...
Effective cotranslational folding of firefly luciferase without chaperones of the Hsp70 family
- Maxim S. Svetlov, Aigar Kommer, Vyacheslav A. Kolb, Alexander S. Spirin
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051752506 (p 242-247)
Abstract Molecular chaperones of the Hsp70 family (bacterial DnaK, DnaJ, and GrpE) were shown to be strictly required for refolding of firefly luciferase from a denatured state and thus for effective restoration of its activity. At the same time the luciferase was found to be synthesized in an Escherichia coli cell‐free translation system in a highly active state in the extract with no chaperone activity. The addition of the chaperones ...
Acid destabilization of the solution conformation of Bcl‐X L does not drive its pH‐dependent insertion into membranes
- Guruvasuthevan R. Thuduppathy, R. Blake Hill
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051807706 (p 248-257)
Abstract Regulation of programmed cell death by Bcl‐xL is dependent on both its solution and integral membrane conformations. A conformational change from solution to membrane is also important in this regulation. This conformational change shows a pH‐dependence similar to the translocation domain of diphtheria toxin, where an acid‐induced molten globule conformation in the absence of lipid vesicles mediates the change from solution...
Determination of network of residues that regulate allostery in protein families using sequence analysis
- Ruxandra I. Dima, D. Thirumalai
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051767306 (p 258-268)
Abstract Allosteric interactions between residues that are spatially apart and well separated in sequence are important in the function of multimeric proteins as well as single‐domain proteins. This observation suggests that, among the residues that are involved in long‐range communications, mutation at one site should affect interactions at a distant site. By adopting a sequence‐based approach, we present an automated approach that...
Crystal structural analysis and metal‐dependent stability and activity studies of the ColE7 endonuclease domain in complex with DNA/Zn 2+
- Lyudmila G. Doudeva, Hsinchin Huang, Kuo‐Chiang Hsia, Zhonghao Shi, Chia‐Lung Li, Yongliang Shen, Yi‐Sheng Cheng, Hanna S. Yuan
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051903406 (p 269-280)
Abstract The nuclease domain of ColE7 (N‐ColE7) contains an H‐N‐H motif that folds in a ββα‐metal topology. Here we report the crystal structures of a Zn2+‐bound N‐ColE7 (H545E mutant) in complex with a 12‐bp duplex DNA and a Ni2+‐bound N‐ColE7 in complex with the inhibitor Im7 at a resolution of 2.5 Å and 2.0 Å, respectively. Metal‐dependent cleavage assays showed that N‐ColE7 cleaves double‐stranded DNA with a single metal ion cofactor, Ni2+,...
S ‐transferase—Structural and mechanistic studies on ligand binding and enzyme inhibition
- Nicole Hiller, Karin Fritz‐Wolf, Marcel Deponte, Wolfgang Wende, Herbert Zimmermann, Katja Becker
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051891106 (p 281-289)
Abstract Glutathione S‐transferase of the malarial parasite Plasmodium falciparum (PfGST) represents a novel class of GST isoenzymes. Since the architecture of the PfGST substrate binding site differs significantly from its human counterparts and there is only this one isoenzyme present in the parasite, PfGST is considered a highly attractive target for antimalarial drug development. Here we report the mechanistic, kinetic, and structural...
Competition between intercellular adhesion molecule‐1 and a small‐molecule antagonist for a common binding site on the αl subunit of lymphocyte function‐associated antigen‐1
- Susan M. Keating, Kevin R. Clark, Lisa D. Stefanich, Fred Arellano, Caroline P. Edwards, Sarah C. Bodary, Steven A. Spencer, Thomas R. Gadek, James C. Marsters, Maureen H. Beresini
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051583406 (p 290-303)
Abstract The lymphocyte function‐associated antigen‐1 (LFA‐1) binding of a unique class of small‐molecule antagonists as represented by compound 3 was analyzed in comparison to that of soluble intercellular adhesion molecule‐1 (sICAM‐1) and A‐286982, which respectively define direct and allosteric competitive binding sites within LFA‐1's inserted (I) domain. All three molecules antagonized LFA‐1 binding to ICAM‐1‐Immunoglobulin G...
Effects of solutes on solubilization and refolding of proteins from inclusion bodies with high hydrostatic pressure
- Seung‐Hyun Lee, John F. Carpenter, Byeong S. Chang, Theodore W. Randolph, Yong‐Sung Kim
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051813506 (p 304-313)
Abstract High hydrostatic pressure (HHP)‐mediated solubilization and refolding of five inclusion bodies (IBs) produced from bacteria, three Gram‐negative binding proteins (GNBP1, GNBP2, and GNBP3) from Drosophila, and two phosphatases from human were investigated in combination of a redox‐shuffling agent (2 mM DTT and 6 mM GSSG) and various additives. HHP (200 MPa) combined with the redox‐shuffling agent resulted in solubilization yields of...
High resolution structure of the HDGF PWWP domain: A potential DNA binding domain
- Stephen M. Lukasik, Tomasz Cierpicki, Matthew Borloz, Jolanta Grembecka, Allen Everett, John H. Bushweller
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051751706 (p 314-323)
Abstract Hepatoma Derived Growth Factor (HDGF) is an endogenous nuclear‐targeted mitogen that is linked with human disease. HDGF is a member of the weakly conserved PWWP domain family. This 70–amino acid motif, originally identified from the WHSC1 gene, has been found in more than 60 eukaryotic proteins. In addition to the PWWP domain, many proteins in this class contain known chromatin remodeling domains, suggesting a role for HDGF in...
Context‐dependent mutations predominate in an engineered high‐affinity single chain antibody fragment
- Katarina S. Midelfort, K. Dane Wittrup
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051842406 (p 324-334)
Abstract A mutational analysis of the femtomolar‐affinity anti‐fluorescein antibody 4M5.3, compared to its wild‐type progenitor, 4‐4‐20, indicates both context‐dependent and ‐independent mutations are responsible for the 1800‐fold affinity improvement. 4M5.3 was engineered from 4‐4‐20 by directed evolution and contains 14 mutations. The seven mutations identified as present in each of 10 final round affinity maturation clones were...
pH driven conformational dynamics and dimer‐to‐monomer transition in DLC8
- P.M. Krishna Mohan, Maneesha Barve, Amarnath Chatterjee, Ramakrishna V. Hosur
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051854906 (p 335-342)
Abstract Dynein light chain protein, a part of the cytoplasmic motor assembly, is a homodimer at physiological pH and dissociates below pH 4.5 to a monomer. The dimer binds to a variety of cargo, whereas the monomer does not bind any of the target proteins. We report here the pH induced stepwise structural and motional changes in the protein, as derived from line broadening and 15N transverse relaxation measurements. At pH 7 and...
Photonic activation of disulfide bridges achieves oriented protein immobilization on biosensor surfaces
- Maria Teresa Neves‐Petersen, Torben Snabe, Søren Klitgaard, Meg Duroux, Steffen B. Petersen
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051885306 (p 343-351)
Abstract Photonic induced immobilization is a novel technology that results in spatially oriented and spatially localized covalent coupling of biomolecules onto thiol‐reactive surfaces. Immobilization using this technology has been achieved for a wide selection of proteins, such as hydrolytic enzymes (lipases/esterases, lysozyme), proteases (human plasminogen), alkaline phosphatase, immunoglobulins' Fab fragment (e.g., antibody...
Finding biologically relevant protein domain interactions: Conserved binding mode analysis
- Benjamin A. Shoemaker, Anna R. Panchenko, Stephen H. Bryant
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.051760806 (p 352-361)
Abstract Proteins evolved through the shuffling of functional domains, and therefore, the same domain can be found in different proteins and species. Interactions between such conserved domains often involve specific, well‐determined binding surfaces reflecting their important biological role in a cell. To find biologically relevant interactions we developed a method of systematically comparing and classifying protein domain...




