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Journal Issue - Volume 17 Issue 1 (January 2008)

Abstract Under appropriate conditions, essentially all proteins are able to aggregate to form long, well‐ordered and β‐sheet‐rich arrays known as amyloid‐like fibrils. These fibrils consist of varying numbers of intertwined protofibrils and can for any given protein exhibit a wealth of different forms at the ultrastructural level. Traditionally, this structural variability or polymorphism has been attributed to differences in the...

Abstract Peptide deformylase (PDF) catalyzes the removal of formyl group from the N‐terminal methionine residues of nascent proteins in prokaryotes, and this enzyme is a high priority target for antibiotic design. In pursuit of delineating the structural–functional features of Escherichia coli PDF (EcPDF), we investigated the mechanistic pathway for the guanidinium chloride (GdmCl)‐induced unfolding of the enzyme by monitoring the...

Abstract Cyclin‐dependent kinase 2 (CDK2) is the most thoroughly studied of the cyclin‐dependent kinases that regulate essential cellular processes, including the cell cycle, and it has become a model for studies of regulatory mechanisms at the molecular level. This contribution identifies flexible and rigid regions of CDK2 based on temperature B‐factors acquired from both X‐ray data and molecular dynamics simulations. In addition, the...

Abstract Acetyl‐CoA carboxylase (ACC) catalyzes the first committed step in the synthesis of long‐chain fatty acids. The crystal structure of the Escherichia coli carboxyltransferase component of ACC revealed an α2β2 subunit composition with two active sites and, most importantly, a unique zinc domain in each αβ pair that is absent in the eukaryotic enzyme. We show here that carboxyltransferase binds DNA. Half‐maximal saturation of different...

Abstract Although the folding of α‐helical repeat proteins has been well characterized, much less is known about the folding of repeat proteins containing β‐sheets. Here we investigate the folding thermodynamics and kinetics of the leucine‐rich repeat (LRR) domain of Internalin B (InlB), an extracellular virulence factor from the bacterium Lysteria monocytogenes. This domain contains seven tandem leucine‐rich repeats, of which each contribute a...

Abstract Metals play a variety of roles in biological processes, and hence their presence in a protein structure can yield vital functional information. Because the residues that coordinate a metal often undergo conformational changes upon binding, detection of binding sites based on simple geometric criteria in proteins without bound metal is difficult. However, aspects of the physicochemical environment around a metal binding site...

Abstract Matrix metalloproteinase 13 (MMP13) is a key enzyme implicated in the degradation of the extracellular matrix in osteoarthritis. Clinical administration of broad spectrum MMP inhibitors such as marimastat has been implicated in severe musculo‐skeletal side effects. Consequently, research has been focused on designing inhibitors that selectively inhibit MMP13, thereby circumventing musculo‐skeletal toxicities. A series of...

Abstract Proteins that can interact with multiple partners play central roles in the network of protein–protein interactions. They are called hub proteins, and recently it was suggested that an abundance of intrinsically disordered regions on their surfaces facilitates their binding to multiple partners. However, in those studies, the hub proteins were identified as proteins with multiple partners, regardless of whether the...

Abstract In this article, we describe a general approach to modeling the structure of binary protein complexes using structural mass spectrometry data combined with molecular docking. In the first step, hydroxyl radical mediated oxidative protein footprinting is used to identify residues that experience conformational reorganization due to binding or participate in the binding interface. In the second step, a three‐dimensional...

Abstract Recombinant human monoclonal antibodies have become important protein‐based therapeutics for the treatment of various diseases. The antibody structure is complex, consisting of β‐sheet rich domains stabilized by multiple disulfide bridges. The dimerization of the CH3 domain in the constant region of the heavy chain plays a pivotal role in the assembly of an antibody. This domain contains a single buried, highly conserved...

Abstract Agitoxin 2 (AgTx2) is a 38‐residue scorpion toxin, cross‐linked by three disulfide bridges, which acts on voltage‐gated K+ (Kv) channels. Maurotoxin (MTX) is a 34‐residue scorpion toxin with an uncommon four‐disulfide bridge reticulation, acting on both Ca2+‐activated and Kv channels. A 39‐mer chimeric peptide, named AgTx2‐MTX, was designed from the sequence of the two toxins and chemically synthesized. It encompasses residues 1–5 of...

Abstract The yeast Ski complex assists the exosome in the degradation of mRNA. The Ski complex consists of three components; Ski2, Ski3, and Ski8, believed to be present in a 1:1:1 stoichiometry. Measuring the mass of intact isolated endogenously expressed Ski complexes by native mass spectrometry we unambiguously demonstrate that the Ski complex has a hetero‐tetrameric stoichiometry consisting of one copy of Ski2 and Ski3 and two...

Abstract The methionine salvage pathway (MSP) plays a crucial role in recycling a sulphahydryl derivative of the nucleoside. Recently, the genes and reactions in MSP from Bacillus subtilis have been identified, where 5‐methylthioribose 1‐phosphate isomerase (M1Pi) catalyzes a conversion of 5‐methylthioribose 1‐phosphate (MTR‐1‐P) to 5‐methylthioribulose 1‐phosphate (MTRu‐1‐P). Herein, we report the crystal structures of B. subtilis M1Pi...

Abstract The Ski complex composed of Ski2p, Ski3p, and Ski8p plays an essential role in the 3′ to 5′ cytoplasmic mRNA degradation pathway in yeast. Ski2p is a putative RNA helicase, belonging in the DExD/H‐box protein families and conserved in eukarya as well as in archaea. The gene product (Ph1280p) from the hyperthermophilic archaeon Pyrococcus horikoshii OT3 shows sequence homology with Ski2p, sharing 22.6% identical amino acids with a...

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