Current Journal Issue - Volume 19 Issue 2 (February 2010)
- In This Issue
- Published in Wiley Interscience on Jan 21, 2010
- DOI: 10.1002/pro.341 (p NA)
No abstract.
- Myoglobin strikes back
- Maurizio Brunori
- Published in Wiley Interscience on Dec 01, 2009
- DOI: 10.1002/pro.300 (p 195-201)
Over the last half century, myoglobin (Mb) has been an excellent model system to test a number of concepts, theories, and new experimental methods that proved valuable to investigate protein structure, function, evolution, and dynamics. Mb's function, most often considered just an oxygen repository, has considerably diversified over the last 15 years, especially because it was shown to have a role in the biochemistry of quenching and synthesizing nitric oxide in the red muscle, thereby...
- Potentially amyloidogenic conformational intermediates populate the unfolding landscape of transthyretin: Insights from molecular dynamics simulations
- J. Rui Rodrigues, Carlos J. V. Simões, Cândida G. Silva, Rui M. M. Brito
- Published in Wiley Interscience on Nov 20, 2009
- DOI: 10.1002/pro.289 (p 202-219)
Protein aggregation into insoluble fibrillar structures known as amyloid characterizes several neurodegenerative diseases, including Alzheimer's, Huntington's and Creutzfeldt-Jakob. Transthyretin (TTR), a homotetrameric plasma protein, is known to be the causative agent of amyloid pathologies such as FAP (familial amyloid polyneuropathy), FAC (familial amyloid cardiomiopathy) and SSA (senile systemic amyloidosis). It is generally accepted that TTR tetramer dissociation and monomer partial...
- pH-dependent stability of neuroserpin is mediated by histidines 119 and 138; Implications for the control of β-sheet A and polymerization
- Didier Belorgey, Peter Hägglöf, Maki Onda, David A. Lomas
- Published in Wiley Interscience on Dec 01, 2009
- DOI: 10.1002/pro.299 (p 220-228)
Neuroserpin is a member of the serpin superfamily. Point mutations in the neuroserpin gene underlie the autosomal dominant dementia, familial encephalopathy with neuroserpin inclusion bodies. This is characterized by the retention of ordered polymers of neuroserpin within the endoplasmic reticulum of neurons. pH has been shown to affect the propensity of several serpins to form polymers. In particular, low pH favors the formation of polymers of both 1-antitrypsin and antithrombin. We report...
- Human tissue transglutaminase is inhibited by pharmacologic and chemical acetylation
- Thung S. Lai, Christopher Davies, Charles S. Greenberg
- Published in Wiley Interscience on Dec 08, 2009
- DOI: 10.1002/pro.301 (p 229-235)
Human tissue transglutaminase (TGM2) is implicated in the pathogenesis of several neurodegenerative disorders including Alzheimer's, Parkinson's and expanded polyglutamine (polyQ) diseases. TGM2 promotes formation of soluble and insoluble high molecular weight aggregates by catalyzing a covalent linkage between peptide-bound Q residues in polyQ proteins and a peptide-bound Lys residue. Therapeutic approaches to modulate the activity of TGM2 are needed to proceed with studies to test the...
- Radiation inactivation of galactose oxidase, a monomeric enzyme with a stable free radical
- Ellis S. Kempner, James W. Whittaker, Jay H. Miller
- Published in Wiley Interscience on Dec 08, 2009
- DOI: 10.1002/pro.302 (p 236-241)
To determine the radiation sensitivity of galactose oxidase, a 68 kDa monomeric enzyme containing a mononuclear copper ion coordinated with an unusually stable cysteinyl-tyrosine (Cys-Tyr) protein free radical. Both active enzyme and reversibly rendered inactive enzyme were irradiated in the frozen state with high-energy electrons. Surviving polypeptides and surviving enzyme activity were analyzed by radiation target theory giving the radiation sensitive mass for each property. In both active...
- Versatile modes of peptide recognition by the ClpX N domain mediate alternative adaptor-binding specificities in different bacterial species
- Tahmeena Chowdhury, Peter Chien, Shamsah Ebrahim, Robert T. Sauer, Tania A. Baker
- Published in Wiley Interscience on Dec 10, 2009
- DOI: 10.1002/pro.306 (p 242-254)
ClpXP, an AAA+ protease, plays key roles in protein-quality control and many regulatory processes in bacteria. The N-terminal domain of the ClpX component of ClpXP is involved in recognition of many protein substrates, either directly or by binding the SspB adaptor protein, which delivers specific classes of substrates for degradation. Despite very limited sequence homology between the E. coli and C. crescentus SspB orthologs, each of these adaptors can deliver substrates to the ClpXP enzyme...
- Mechanism of glyceraldehyde-3-phosphate dehydrogenase inactivation by tyrosine nitration
- Vikram Palamalai, Masaru Miyagi
- Published in Wiley Interscience on Dec 15, 2009
- DOI: 10.1002/pro.311 (p 255-262)
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifaceted protein that is involved in numerous processes including glycolysis, translational silencing, transcriptional regulation of specific genes, and acting as a nitric oxide sensor. The precise mechanism on how GAPDH is targeted to these different roles is unclear but believed to involve specific posttranslational modification to the protein. Numerous studies have demonstrated that GAPDH is a target for tyrosine nitration. However,...
- Cyclic voltammetry: A new strategy for the evaluation of oxidative damage to bovine insulin
- Wansong Zong, Rutao Liu, Feng Sun, Meijie Wang, Pengjun Zhang, Yihong Liu, Yanmin Tian
- Published in Wiley Interscience on Dec 21, 2009
- DOI: 10.1002/pro.313 (p 263-268)
Research on protein oxidative damage may give insight into the nature of protein functions and pathological conditions. In this work, the oxidative damage of bovine insulin on Au electrode was investigated by cyclic voltammetry (CV). The experimental results show that there are two anodic peaks for the oxidative damage of bovine insulin, which arise from the oxidation of the exposed disulfide bond SSCYS7A,CYS7B, forming sulfenic acid RSOH (1.20 V, vs. SCE), sulfinic acid RSO2H and sulfonic acid...
- Osmolytes modulate conformational exchange in solvent-exposed regions of membrane proteins
- Ricardo H. Flores Jiménez, Marie-Ange Do Cao, Miyeon Kim, David S. Cafiso
- Published in Wiley Interscience on Dec 10, 2009
- DOI: 10.1002/pro.305 (p 269-278)
Site-directed spin labeling (SDSL) was used to investigate local structure and conformational exchange in two bacterial outer-membrane TonB-dependent transporters, BtuB and FecA. Protecting osmolytes, such as polyethylene glycols (PEGs) are known to modulate a substrate-dependent conformational equilibrium in the energy coupling motif (Ton box) of BtuB. Here, we demonstrate that a segment that is N-terminal to the Ton box in BtuB, is in conformational exchange between ordered and disordered...
- Aggregation of a multidomain protein: A coagulation mechanism governs aggregation of a model IgG1 antibody under weak thermal stress
- Christian Beyschau Andersen, Mauro Manno, Christian Rischel, Matthías Thórólfsson, Vincenzo Martorana
- Published in Wiley Interscience on Dec 15, 2009
- DOI: 10.1002/pro.309 (p 279-290)
Using an IgG1 antibody as a model system, we have studied the mechanisms by which multidomain proteins aggregate at physiological pH when incubated at temperatures just below their lowest thermal transition. In this temperature interval, only minor changes to the protein conformation are observed. Light scattering consistently showed two coupled phases: an initial fast phase followed by several hours of exponential growth of the scattered intensity. This is the exact opposite of the lag-time...
- Elucidating residue roles in engineered variants of AraC regulatory protein
- Shuang-Yan Tang, Patrick C. Cirino
- Published in Wiley Interscience on Dec 15, 2009
- DOI: 10.1002/pro.310 (p 291-298)
The AraC regulatory protein was previously engineered to control gene expression specifically in response to D-arabinose and not the native effector L-arabinose (Tang et al., J Am Chem Soc 2008;130:5267-5271). Mutations were targeted in the ligand-binding pocket and on the AraC N-terminal arm, which plays an important role in maintaining repressing or activating conformations in the absence or presence of effector, respectively. In this study, we analyze the contributions of individual...
- Germline humanization of a murine Aβ antibody and crystal structure of the humanized recombinant Fab fragment
- Remy Robert, Victor A. Streltsov, Janet Newman, Lesley A. Pearce, Kim L. Wark, Olan Dolezal
- Published in Wiley Interscience on Dec 15, 2009
- DOI: 10.1002/pro.312 (p 299-308)
Alzheimer's disease is the most common form of dementia, affecting 26 million people worldwide. The A peptide (39-43 amino acids) derived from the proteolytic cleavage of the amyloid precursor protein is one of the main constituents of amyloid plaques associated with disease pathogenesis and therefore a validated target for therapy. Recently, we characterized antibody fragments (Fab and scFvs) derived from the murine monoclonal antibody WO-2, which bind the immunodominant epitope (3EFRH6) in...
- Mobile loop mutations in an archaeal inositol monophosphatase: Modulating three-metal ion assisted catalysis and lithium inhibition
- Zheng Li, Kimberly A. Stieglitz, Anthony L. Shrout, Yang Wei, Robert M. Weis, Boguslaw Stec, Mary F. Roberts
- Published in Wiley Interscience on Dec 21, 2009
- DOI: 10.1002/pro.315 (p 309-318)
The inositol monophosphatase (IMPase) enzyme from the hyperthermophilic archaeon Methanocaldococcus jannaschii requires Mg2+ for activity and binds three to four ions tightly in the absence of ligands: KD = 0.8 M for one ion with a KD of 38 M for the other Mg2+ ions. However, the enzyme requires 5-10 mM Mg2+ for optimum catalysis, suggesting substrate alters the metal ion affinity. In crystal structures of this archaeal IMPase with products, one of the three metal ions is coordinated by only...
- Crystal structure of a super leucine zipper, an extended two-stranded super long coiled coil
- Jiasheng Diao
- Published in Wiley Interscience on Dec 21, 2009
- DOI: 10.1002/pro.316 (p 319-326)
Coiled coil is a ubiquitous structural motif in proteins, with two to seven alpha helices coiled together like the strands of a rope, and coiled coil folding and assembly is not completely understood. A GCN4 leucine zipper mutant with four mutations of K3A, D7A, Y17W, and H18N has been designed, and the crystal structure has been determined at 1.6 Å resolution. The peptide monomer shows a helix trunk with short curved N- and C-termini. In the crystal, two monomers cross in 35° and form an...



