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Journal Issue - Volume 15 Issue 6 (June 2006)

Abstract The hydroxyl group of a serine residue at position 195 acts as a nucleophile in the catalytic mechanism of the serine proteases. However, the chemically similar residue, threonine, is rarely used in similar functional context. Our structural modeling suggests that the Ser 195 → Thr trypsin variant is inactive due to negative steric interaction between the methyl group on the β‐carbon of Thr 195 and the disulfide bridge...

Abstract Folding and self‐assembly of the 42‐residue amyloid β‐protein (Aβ) are linked to Alzheimer's disease (AD). The 21–30 region of Aβ, Aβ(21–30), is resistant to proteolysis and is believed to nucleate the folding of full‐length Aβ. The conformational space accessible to the Aβ(21–30) peptide is investigated by using replica exchange molecular dynamics simulations in explicit solvent. Conformations belonging to the global free...

Abstract Ubiquitin is an important cellular signal that targets proteins for degradation or regulates their functions. The previously identified BMSC‐UbP protein derived from bone marrow stromal cells contains a ubiquitin‐associated (UBA) domain at the C terminus that has been implicated in linking cellular processes and the ubiquitin system. Here, we report the solution NMR structure of the UBA domain of human BMSC‐UbP protein and...

Abstract The structural basis for the coupling of ATP binding and hydrolysis to chaperone activity remains a central question in Hsp90 biology. By analogy to MutL, ATP binding to Hsp90 is thought to promote intramolecular N‐terminal dimerization, yielding a molecular clamp functioning in substrate protein activation. Though observed in studies with recombinant domains, whether such quaternary states are present in native Hsp90s is...

Abstract The ATPase activity of many types of molecular chaperones is stimulated by polypeptide substrate binding via molecular mechanisms that are, for the most part, unknown. Here, we report that such stimulation of the ATPase activity of GroEL is abolished when its conserved apical domain residue Glu257 is replaced by alanine. This mutation is also found to convert the ATPase profile of GroEL, a group I chaperonin, into one that...

Abstract The “mu loop,” an 11‐residue loop spanning amino acid residues 33–43, is a characteristic structural feature of the mu class of glutathione transferases. To assess the contribution of the mu loop to the structure and function of rat GST M1‐1, amino acid residues 35–44 (35GDAPDYDRSQ44) were excised by deletion mutagenesis, resulting in the “Deletion Enzyme.” Kinetic studies reveal that the Km values of the Deletion Enzyme are markedly...

Abstract The signal recognition particle (SRP) plays an important role in the delivery of secretory proteins to cellular membranes. Mammalian SRP is composed of six polypeptides among which SRP68 and SRP72 form a heterodimer that has been notoriously difficult to investigate. Human SRP68 was purified from overexpressing Escherichia coli cells and was found to bind to recombinant SRP72 as well as in vitro‐transcribed human SRP RNA. Polypeptide...

Abstract Recent work using chemical cross‐linking to define interresidue distance constraints in proteins has shown that these constraints are useful for testing tertiary structural models. We applied this approach to the G‐protein‐coupled receptor bovine rhodopsin in its native membrane using lysine‐ and cysteine‐targeted bifunctional cross‐linking reagents. Cross‐linked proteolytic peptides of rhodopsin were identified by combined...

Abstract A new computational approach has been developed to determine the spatial arrangement of proteins in membranes by minimizing their transfer energies from water to the lipid bilayer. The membrane hydrocarbon core was approximated as a planar slab of adjustable thickness with decadiene‐like interior and interfacial polarity profiles derived from published EPR studies. Applicability and accuracy of the method was verified for a...

Abstract Despite possessing a common cross‐β core, amyloid fibrils are known to exhibit great variations in their morphologies. To date, the mechanism responsible for the polymorphism in amyloid fibrils is poorly understood. Here we report that two variants of mammalian full‐length prion protein (PrP), hamster (Ha) and mouse (Mo) PrPs, produced morphologically distinguishable subsets of mature fibrils under identical solvent...

Abstract Flaviviruses cause many human diseases, including dengue fever, yellow fever, West Nile viral encephalitis, and hemorrhagic fevers, and are transmitted to their vertebrate hosts by infected mosquitoes and ticks. Domain III of the envelope protein (E‐D3) is considered to be the primary viral determinant involved in the virus–host‐cell receptor interaction, and thus represents an excellent target for antiviral drug...

Abstract (R)‐ and (S)‐dichlorprop/α‐ketoglutarate dioxygenases (RdpA and SdpA) catalyze the oxidative cleavage of 2‐(2,4‐dichlorophenoxy)propanoic acid (dichlorprop) and 2‐(4‐chloro‐2‐methyl‐phenoxy)propanoic acid (mecoprop) to form pyruvate plus the corresponding phenol concurrent with the conversion of α‐ketoglutarate (αKG) to succinate plus CO2. RdpA and SdpA are strictly enantiospecific, converting only the (R) or the (S) enantiomer,...

Abstract The NADP‐reducing hydrogenase complex from Desulfovibrio fructosovorans is a heterotetramer encoded by the hndABCD operon. Sequence analysis indicates that the HndC subunit (52 kDa) corresponds to the NADP‐reducing unit, and the HndD subunit (63.5 kDa) is homologous to Clostridium pasteurianum hydrogenase. The role of HndA and HndB subunits (18.8 kDa and 13.8 kDa, respectively) in the complex remains unknown. The HndA subunit belongs...

Abstract The general secretory, Sec, system translocates precursor polypeptides from the cytosol across the cytoplasmic membrane in Escherichia coli. SecB, a small cytosolic chaperone, captures the precursor polypeptides before they fold and delivers them to the membrane translocon through interactions with SecA. Both SecB and SecA display twofold symmetry and yet the complex between the two is stabilized by contacts that are...

Abstract Aldehyde dehydrogenases are general detoxifying enzymes, but there are also isoenzymes that are involved in specific metabolic pathways in different organisms. Two of these enzymes are Escherichia coli lactaldehyde (ALD) and phenylacetaldehyde dehydrogenases (PAD), which participate in the metabolism of fucose and phenylalanine, respectively. These isozymes share some properties with the better characterized mammalian enzymes but have...

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