Abstract:
:Thiol peroxidases (Tpxs) are dimeric 2-Cys peroxiredoxins from bacteria that preferentially reduce alkyl hydroperoxides. Catalysis requires two conserved residues, the peroxidatic cysteine and the resolving cysteine, which are located in helix alpha(2) and helix alpha(3), respectively. The partial unraveling of helices alpha(2) and alpha(3) during catalysis allows for the formation of an intramolecular disulfide between these two residues. Here, we present three structures of Escherichia coli Tpx representing the fully folded (peroxide binding site intact), locally unfolded (disulfide bond), and partially locally unfolded (transitional state) conformations. We also compare known Tpx crystal structures and analyze the sequence-conservation patterns among nearly 300 Tpx sequences. Twelve fully conserved Tpx-specific residues cluster at the active site and dimer interface, and an additional 37 highly conserved residues are mostly located in a cradle providing the environment for helix alpha(2). Using the structures determined here as representative fully folded, transitional, and locally unfolded Tpx conformations, we describe in detail the structural changes associated with catalysis in the Tpx subfamily. Key insights include the description of a conserved hydrophobic collar around the active site, a set of conserved packing interactions between helices alpha(2) and alpha(3) that allow the local unfolding of alpha(2) to trigger the partial unfolding of alpha(3), a conserved dimer interface that anchors the ends of helices alpha(2) and alpha(3) to stabilize the active site during structural transitions, and a conserved set of residues constituting a cradle that stabilizes the two discrete conformations of helix alpha(2) involved in catalysis. The involvement of the dimer interface in stabilizing active-site folding and in forming the hydrophobic collar implies that Tpx is an obligate homodimer and explains the high conservation of interface residues.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Hall A,Sankaran B,Poole LB,Karplus PAdoi
10.1016/j.jmb.2009.08.040subject
Has Abstractpub_date
2009-11-06 00:00:00pages
867-81issue
4eissn
0022-2836issn
1089-8638pii
S0022-2836(09)01042-0journal_volume
393pub_type
杂志文章abstract::Biogenesis of β-barrel membrane proteins is a complex, multistep, and as yet incompletely characterized process. The bacterial porin family is perhaps the best-studied protein family among β-barrel membrane proteins that allows diffusion of small solutes across the bacterial outer membrane. In this study, we have iden...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2012.02.043
更新日期:2012-05-25 00:00:00
abstract::The intergenic region in the genome of the Ff class of filamentous phage (comprising strains fl, fd and M13) genome constitutes 8% of the viral genome, and has essential functions in DNA replication and phage morphogenesis. The functional domains of this region may be inserted into separate sites of a plasmid to funct...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(92)90858-h
更新日期:1992-12-05 00:00:00
abstract::The intermembrane space of mitochondria contains a dedicated chaperone network-the small translocase of the inner membrane (TIM) family-for the sorting of hydrophobic precursors. All small TIMs are defined by the presence of a twin CX(3)C motif and the monomeric proteins are stabilized by two intramolecular disulfide ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2012.09.019
更新日期:2012-12-14 00:00:00
abstract::Neurogenesis depends on exquisitely regulated interactions between macromolecules on the cell surface and in the extracellular matrix. In particular, interactions between proteoglycans and members of the type IIa subgroup of receptor protein tyrosine phosphatases underlie crucial developmental processes such as the fo...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2011.03.013
更新日期:2011-05-13 00:00:00
abstract::Heterocyst-forming cyanobacteria have multiple genes encoding proteins that are similar to the RNP family of eukaryotic RNA-binding proteins. Three genes from two strains of cyanobacteria (Anabaena and Chlorogloeopsis) have been sequenced. All three putative gene products contain a single RNA Recognition Motif (RRM) t...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1994.1070
更新日期:1994-01-21 00:00:00
abstract::The morphogene bolA is a general stress response gene in Escherichia coli that induces a round morphology when overexpressed. Results presented in this report show that increased BolA levels can inhibit cell elongation mechanisms. MreB polymerization is crucial for the bacterial cell cytoskeleton, and this protein is ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2008.12.026
更新日期:2009-02-06 00:00:00
abstract::We have developed an in vitro selection procedure to elucidate the specificity of RecA assisted oligonucleotide recognition of double stranded DNA. The procedure was based on formation of a synaptic complex between an oligonucleotide-RecA filament and a supercoiled plasmid bearing a homologous partially degenerate reg...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.1164
更新日期:1997-08-15 00:00:00
abstract::An understanding of the structural basis for protein-protein interactions, and molecular recognition in general, requires complete characterization of binding energetics. Not only does this include quantification of the changes that occur in all of the thermodynamic parameters upon binding, including the enthalpy, ent...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.0977
更新日期:1997-05-02 00:00:00
abstract::The vicinal amide proton-C alpha proton spin-spin coupling constants, JHN alpha, in the globular protein basic pancreatic trypsin inhibitor (BPTI) have been measured using phase-sensitive correlated spectroscopy at high digital resolution. In conjunction with the crystal structure of BPTI, these data were used to cali...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(84)90035-4
更新日期:1984-12-15 00:00:00
abstract::Crystals of the catalytic domain of human fibroblast collagenase have been grown in the presence and absence of an inhibitor. Crystals of the inhibitor complex grew from 0.2 M ammonium sulfate and 15 to 30% PEG 8000 at 22 degrees C as bipyramids in the space group P6(2) or P6(4). Crystals of the unligated enzyme grew ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(94)90068-x
更新日期:1994-03-11 00:00:00
abstract::The structure and backbone dynamics of a double labelled (15N,13C) monomeric, 23.7 kD phosphoglycerate mutase (PGAM) from Schizosaccharomyces pombe have been investigated in solution using NMR spectroscopy. A set of 3125 NOE-derived distance restraints, 148 restraints representing inferred hydrogen bonds and 149 value...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2000.4390
更新日期:2001-02-16 00:00:00
abstract::The solution structure of the 96-residue C-terminal fragment of the merozoite surface protein 1 (MSP-1) from Plasmodium falciparum has been determined using nuclear magnetic resonance (NMR) spectroscopic measurements on uniformly13C/15N-labelled protein, efficiently expressed in the methylotrophic yeast Komagataella (...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1999.2753
更新日期:1999-05-28 00:00:00
abstract::Ground-state dynamics in RNA is a critical precursor for structural adaptation observed ubiquitously in protein-RNA recognition. A tertiary conformational analysis of the stem-loop structural element in the transactivation response element (TAR) from human immunodeficiency virus type 1 (HIV-I) RNA is presented using r...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2001.5235
更新日期:2002-01-11 00:00:00
abstract::The effect of GT/CA dinucleotide repeat tracts on RecA-dependent homologous recombination was examined in vitro. By measuring the binding of RecA protein to oligonucleotides containing GT or CA repeats using the surface plasmon resonance (BIAcore), we show that the efficiency of RecA protein binding is sequence depend...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.1293
更新日期:1997-10-17 00:00:00
abstract::The dielectric constants of sickle cell hemoglobin were determined before and after gelation. The dielectric properties of oxy and deoxy sickle cell hemoglobin in solution are nearly identical to those of oxy and deoxy hemoglobin A. Only in the gel state did deoxy sickle cell hemoglobin display dielectric behavior dif...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(83)80307-6
更新日期:1983-08-15 00:00:00
abstract::Mycobacteriophage Brujita is an unusual temperate phage in which establishment of superinfection immunity is dependent on chromosomal integration. Integration is mediated by a non-canonical tyrosine integrase (Int) lacking an N-terminal domain typically associated with binding to arm-type sites within the phage attach...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2016.04.023
更新日期:2016-06-05 00:00:00
abstract::We reported recently that activation of the inositol 1,4,5-triphosphate receptor (IP3R) is required for efficient HIV-1 Gag trafficking and viral particle release. IP3R activation requires phospholipase C (PLC)-catalyzed hydrolysis of PI(4,5)P(2) to IP3 and diacylglycerol. We show that Sprouty2 (Spry2), which binds PI...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2011.04.069
更新日期:2011-07-22 00:00:00
abstract::alpha-Lactalbumin, a small calcium-binding protein, forms an equilibrium molten globule state under a variety of conditions. A set of four peptides designed to probe the role of local interactions and the role of potential long-range interactions in stabilizing the molten globule of alpha-lactalbumin has been prepared...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.2099
更新日期:1998-01-01 00:00:00
abstract::RNA polymerase II (Pol II) and its general transcription factors assemble on the promoters of mRNA genes to form large macromolecular complexes that initiate transcription in a regulated manner. During early transcription, these complexes undergo dynamic rearrangement and disassembly as Pol II moves away from the star...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2020.05.005
更新日期:2020-06-26 00:00:00
abstract::The disulphide active sites of thioredoxin and DsbA are known to possess a high degree of structural homology. However, DsbA is a much stronger oxidant than thioredoxin. The redox potential difference between DsbA and thioredoxin has been measured to be 160 mV, equivalent to a shift of 15.4 kJ/mol in the reduced/oxidi...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1995.0303
更新日期:1995-06-02 00:00:00
abstract::The secondary structure of ribonuclease T1 (RNase T1) in aqueous solution and its temperature-induced structural changes have been investigated by Fourier-transform infrared (FT-IR) spectroscopy. 13 to 14% alpha-helix and 32 to 33% beta-sheet were estimated from the resolution-enhanced FT-IR spectra, in agreement with...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1993.1442
更新日期:1993-08-05 00:00:00
abstract::The soluble domain of the self-assembly vaccinia virus envelope protein A27L, sA27L-aa, consists of a flexible extended coil at the N terminus and a rigid hydrophobic coiled-coil region at the C terminus. In the former, a basic strip of 12 residues is responsible for binding to cell-surface heparan sulfates. Although ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.04.024
更新日期:2005-06-24 00:00:00
abstract::The structure of the recombinant (-) gamma-lactamase from an Aureobacterium species has been solved at 1.73A resolution in the cubic space group F23 with unit cell parameters a=b=c=240.6A. The trimeric enzyme has an alpha/beta hydrolase fold and closely resembles the cofactor free haloperoxidases. The structure has be...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2004.03.001
更新日期:2004-04-30 00:00:00
abstract::Salmonellais a foodborne pathogen that causes annually millions of cases of salmonellosis globally, yet Salmonella-specific antibacterials are not available. During inflammation, Salmonella utilizes the Amadori compound fructose-asparagine (F-Asn) as a nutrient through the successive action of three enzymes, including...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2019.08.017
更新日期:2019-11-08 00:00:00
abstract::Using a lacI-Z fusion system, we have determined the efficiency of suppression of nonsense codons in the I gene of Escherichia coli by assaying beta-galactosidase activity. We examined the efficiency of four amber suppressors acting on 42 different amber (UAG) codons at known positions in the I gene, and the efficienc...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(83)90087-6
更新日期:1983-02-15 00:00:00
abstract::WNK1 [with no lysine (K)-1] is a 250-kDa serine/threonine protein kinase involved in the maintenance of cellular salt levels and is directly linked to a hereditary form of hypertension. Here, we report the solution NMR structure of the autoinhibitory domain of WNK1 (WNK1-AI), a small regulatory subunit that lies immed...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2013.01.031
更新日期:2013-04-26 00:00:00
abstract::The catalytic or functionally important residues of a protein are known to exist in evolutionarily constrained regions. However, the patterns of residue conservation alone are sometimes not very informative, depending on the homologous sequences available for a given query protein. Here, we present an integrated metho...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(03)00207-9
更新日期:2003-04-11 00:00:00
abstract::Folding kinetics of large RNAs are just beginning to be investigated. We show that the Tetrahymena self-splicing RNA partitions into a population that rapidly reaches the native state, and a slowly folding population that is trapped in metastable misfolded structures. Transitions from the misfolded structures to the n...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.1311
更新日期:1997-10-17 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific mediator of angiogenesis and vasculogenesis. VEGF is involved pathologically in cancer, proliferative retinopathy and rheumatoid arthritis, and as such represents an important therapeutic target. Three classes of disulfide-constrained pept...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2001.5370
更新日期:2002-02-22 00:00:00
abstract::GTP and Ca2+, two well-known modulators of intracellular signaling pathways, control a structural/functional switch between two vital and mutually exclusive activities, cross-linking and Galpha activity, in the same enzyme. The enzyme, a brain-derived tissue-type transglutaminase (TGase), was recently cloned by us in ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.2052
更新日期:1998-10-02 00:00:00