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Current Journal Issue - Volume 19 Issue 9 (September 2010)

  • In this issue
  • Published in Wiley Online Library on Jun 15, 2010
  • DOI: 10.1002/pro.478 (p )

Abstract Aggregation of human therapeutic antibodies represents a significant hurdle to product development. In a test across multiple antibodies, it was observed that IgG1 antibodies aggregated less, on average, than IgG2 antibodies under physiological pH and mildly elevated temperature. This phenomenon was also observed for IgG1 and IgG2 subclasses of anti‐streptavidin, which shared 95% sequence identity but varied in interchain...

Abstract The original signature of the transferrin (TF) family of proteins was the ability to bind ferric iron with high affinity in the cleft of each of two homologous lobes. However, in recent years, new family members that do not bind iron have been discovered. One new member is the inhibitor of carbonic anhydrase (ICA), which as its name indicates, binds to and strongly inhibits certain isoforms of carbonic anhydrase. Recently,...

Abstract Dipeptidyl peptidase IV (DPP‐IV) is a drug target in the treatment of human type II diabetes. It is a type II membrane protein with a single transmembrane domain (TMD) anchoring the extracellular catalytic domain to the membrane. DPP‐IV is active as a dimer, with two dimer interacting surfaces located extracellularly. In this study, we demonstrate that the TM of DPP‐IV promotes DPP‐IV dimerization and rescues monomeric...

Abstract Protein adsorption on a surface plays an important role in biomaterial science and medicine. It is strongly related to the interaction between the protein residues and the surface. Here we report all‐atom molecular dynamics simulations of the adsorption of an ionic complementary peptide, EAK16‐II, to the hydrophobic highly ordered pyrolytic graphite surface. We find that, the hydrophobic interaction is the main force to...

Abstract The antiviral lectin scytovirin (SVN) contains a total of five disulfide bonds in two structurally similar domains. Previous reports provided contradictory results on the disulfide pairing in each individual domain, and we have now re‐examined the disulfide topology. N‐terminal sequencing and mass spectrometry were used to analyze proteolytic fragments of native SVN obtained at acidic pH, yielding the assignment as...

Abstract The aim of this article is to analyze conformational changes by comparing 10 different structures of Pseudomonas aeruginosa phosphomannomutase/phosphoglucomutase (PMM/PGM), a four‐domain enzyme in which both substrate binding and catalysis require substantial movement of the C‐terminal domain. We focus on changes in interdomain and active site crevices using a method called computational solvent mapping rather than superimposing the...

thumbnail image: Three‐dimensional structure of the weakly associated protein homodimer SeR13 using RDCs and paramagnetic surface mapping

Abstract The traditional NMR‐based method for determining oligomeric protein structure usually involves distinguishing and assigning intra‐ and intersubunit NOEs. This task becomes challenging when determining symmetric homo‐dimer structures because NOE cross‐peaks from a given pair of protons occur at the same position whether intra‐ or intersubunit in origin. While there are isotope‐filtering strategies for distinguishing intra...

Abstract α‐Synuclein function is thought to be related to its membrane binding ability. Solution NMR studies have identified several α‐synuclein‐membrane interaction modes in small unilamellar vesicles (SUVs), but how membrane properties affect binding remains unclear. Here, we use 19F NMR to study α‐synuclein‐membrane interactions by using 3‐fluoro‐L‐tyrosine (3FY) and trifluoromethyl‐L‐phenylalanine (tfmF) labeled proteins. Our results...

Abstract Mycobacterium tuberculosis encodes five gene clusters (ESX‐1 to ESX‐5) for Type VII protein secretion systems that are implicated in mycobacterial pathogenicity. Substrates for the secretion apparatus are encoded within the gene clusters and in additional loci that lack the components of the secretion apparatus. The best characterized substrates are the ESX complexes, 1:1 heterodimers of ESAT‐6 and CFP‐10, the prototypical...

Abstract Peripheral subunit binding domains (PSBDs) are integral parts of large multienzyme complexes involved in carbohydrate metabolism. PSBDs facilitate shuttling of prosthetic groups between different catalytic subunits. Their protein surface is characterized by a high density of positive charges required for binding to subunits within the complex. Here, we investigated folding thermodynamics and kinetics of the human PSBD...

Abstract The molecular basis of resistance to β‐lactams and β‐lactam‐β‐lactamase inhibitor combinations in the KPC family of class A enzymes is of extreme importance to the future design of effective β‐lactam therapy. Recent crystal structures of KPC‐2 and other class A β‐lactamases suggest that Ambler position Trp105 may be of importance in binding β‐lactam compounds. Based on this notion, we explored the role of residue Trp105 in...

Abstract The human neuronal Cys‐loop ligand‐gated ion channel superfamily of ion channels are important determinants of human behavior and the target of many drugs. It is essential for their structural characterization to achieve high‐level expression in a functional state. The aim of this work was to establish stable mammalian cell lines that enable high‐level heterologous production of pure receptors in a state that supports...

Abstract Glycosylation is essential to the maintenance of protein quality in the vesicular protein trafficking pathway in eukaryotic cells. Using the yeast multicopper oxidase, Fet3p, the hypothesis is tested that core glycosylation suppresses Fet3p nascent chain aggregation during synthesis into the endoplasmic reticulum (ER). Fet3p has 11 crystallographically mapped N‐linked core glycan units. Assembly of four of these units is...

Abstract We here report for the first time the creation of prostate specific antigen (PSA) and Fab anti‐PSA biosensor arrays using UV light‐assisted molecular immobilization (LAMI), aiming at the detection and quantification of PSA, a cancer marker. The technology involves formation of free, reactive thiol groups upon UV excitation of protein aromatic residues located in spatial proximity of disulphide bridges, a conserved...

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