Modulating Functional Loop Movements: The Role of Highly Conserved Residues in the Correlated Loop Motions

ChemBioChem ◽  
2004 ◽  
Vol 5 (2) ◽  
pp. 224-230 ◽  
Author(s):  
Kannan Gunasekaran ◽  
Ruth Nussinov
Keyword(s):  
Conserved Residues ◽  
Loop Motions

The Role of Conserved Residues in the DEDDh Motif: the Proton-Transfer Mechanism of HIV-1 RNase H

ACS Catalysis ◽  
2021 ◽  
pp. 7915-7927
Author(s):  
Simon L. Dürr ◽  
Olga Bohuszewicz ◽  
Dénes Berta ◽  
Reynier Suardiaz ◽  
Pablo G. Jambrina ◽  
...  
Keyword(s):  
Proton Transfer ◽  
Rnase H ◽  
Transfer Mechanism ◽  
Conserved Residues ◽  
Hiv 1

scholarly journals Effects of Amino Acid Substitutions at Conserved and Acidic Residues within Region 1.1 of Escherichia coli ς70

2000 ◽  
Vol 182 (1) ◽  
pp. 221-224 ◽  
Author(s):  
Christina Wilson Bowers ◽  
Andrea McCracken ◽  
Alicia J. Dombroski
Keyword(s):  
Escherichia Coli ◽  
Amino Acid ◽  
Aspartic Acid ◽  
Transcription Initiation ◽  
Amino Acid Substitutions ◽  
Conserved Residues ◽  
Acidic Residues

ABSTRACT Amino acid substitutions in Escherichia coliς70 were generated and characterized in an analysis of the role of region 1.1 in transcription initiation. Several acidic and conserved residues are tolerant of substitution. However, replacement of aspartic acid 61 with alanine results in inactivity caused by structural and functional thermolability.

scholarly journals Role of group-conserved residues in the helical core of beta2-adrenergic receptor

2007 ◽  
Vol 104 (17) ◽  
pp. 7027-7032 ◽  
Author(s):  
P. Chelikani ◽  
V. Hornak ◽  
M. Eilers ◽  
P. J. Reeves ◽  
S. O. Smith ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Conserved Residues

scholarly journals The role of conserved residues in Fdc decarboxylase in prenylated flavin mononucleotide oxidative maturation, cofactor isomerization, and catalysis

2017 ◽  
Vol 293 (7) ◽  
pp. 2272-2287 ◽  
Author(s):  
Samuel S. Bailey ◽  
Karl A. P. Payne ◽  
Karl Fisher ◽  
Stephen A. Marshall ◽  
Matthew J. Cliff ◽  
...  
Keyword(s):  
Flavin Mononucleotide ◽  
Conserved Residues

scholarly journals GlcNAcstatins are nanomolar inhibitors of human O-GlcNAcase inducing cellular hyper-O-GlcNAcylation

2009 ◽  
Vol 420 (2) ◽  
pp. 221-227 ◽  
Author(s):  
Helge C. Dorfmueller ◽  
Vladimir S. Borodkin ◽  
Marianne Schimpl ◽  
Daan M. F. van Aalten
Keyword(s):  
Active Site ◽  
Cell Biology ◽  
Rational Design ◽  
Catalytic Mechanism ◽  
Conserved Residues ◽  
Cellular Processes ◽  
Acetyl Group ◽  
Nanomolar Range ◽  
Insight Into

O-GlcNAcylation is an essential, dynamic and inducible post-translational glycosylation of cytosolic proteins in metazoa and can show interplay with protein phosphorylation. Inhibition of OGA (O-GlcNAcase), the enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, is a useful strategy to probe the role of this modification in a range of cellular processes. In the present study, we report the rational design and evaluation of GlcNAcstatins, a family of potent, competitive and selective inhibitors of human OGA. Kinetic experiments with recombinant human OGA reveal that the GlcNAcstatins are the most potent human OGA inhibitors reported to date, inhibiting the enzyme in the sub-nanomolar to nanomolar range. Modification of the GlcNAcstatin N-acetyl group leads to up to 160-fold selectivity against the human lysosomal hexosaminidases which employ a similar substrate-assisted catalytic mechanism. Mutagenesis studies in a bacterial OGA, guided by the structure of a GlcNAcstatin complex, provides insight into the role of conserved residues in the human OGA active site. GlcNAcstatins are cell-permeant and, at low nanomolar concentrations, effectively modulate intracellular O-GlcNAc levels through inhibition of OGA, in a range of human cell lines. Thus these compounds are potent selective tools to study the cell biology of O-GlcNAc.

scholarly journals The role of RelA (p65) threonine 505 phosphorylation in the regulation of cell growth, survival, and migration

2011 ◽  
Vol 22 (17) ◽  
pp. 3032-3040 ◽  
Author(s):  
Aichi Msaki ◽  
Ana M. Sánchez ◽  
Li Fang Koh ◽  
Benjamin Barré ◽  
Sonia Rocha ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Cellular Migration ◽  
Negative Regulator ◽  
Drug Induced ◽  
Conserved Residues ◽  
Cellular Processes ◽  
And Migration ◽  
Induced Apoptosis ◽  
Proliferation And Migration

The NF-κB family of transcription factors is a well-established regulator of the immune and inflammatory responses and also plays a key role in other cellular processes, including cell death, proliferation, and migration. Conserved residues in the trans-activation domain of RelA, which can be posttranslationally modified, regulate divergent NF-κB functions in response to different cellular stimuli. Using rela−/−mouse embryonic fibroblasts reconstituted with RelA, we find that mutation of the threonine 505 (T505) phospho site to alanine has wide-ranging effects on NF-κB function. These include previously described effects on chemotherapeutic drug-induced apoptosis, as well as new roles for this modification in autophagy, cell proliferation, and migration. This last effect was associated with alterations in the actin cytoskeleton and expression of cellular migration–associated genes such as WAVE3 and α-actinin 4. We also define a new component of cisplatin-induced, RelA T505–dependent apoptosis, involving induction of NOXA gene expression, an effect explained at least in part through induction of the p53 homologue, p73. Therefore, in contrast to other RelA phosphorylation events, which positively regulate NF-κB function, we identified RelA T505 phosphorylation as a negative regulator of its ability to induce diverse cellular processes such as apoptosis, autophagy, proliferation, and migration.

scholarly journals Insights into substrate binding and catalysis in bacterial type I dehydroquinase

2014 ◽  
Vol 462 (3) ◽  
pp. 415-424 ◽  
Author(s):  
María Maneiro ◽  
Antonio Peón ◽  
Emilio Lence ◽  
José M. Otero ◽  
Mark J. Van Raaij ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Substrate Binding ◽  
Detailed Knowledge ◽  
Type I ◽  
Conserved Residues ◽  
Binding Process ◽  
Bacterial Type

The crystal structure of S. typhi type I dehydroquinase in complex with (2R)-3-methyl-3-dehydroquinic acid is described. A previously unknown key role of several conserved residues and a detailed knowledge of the substrate binding process is detailed.

Biochemistry and site-directed mutational analysis of Δ7-sterol-C5(6)-desaturase

2000 ◽  
Vol 28 (6) ◽  
pp. 799-803 ◽  
Author(s):  
A. Rahier ◽  
P. Benveniste ◽  
T. Husselstein ◽  
M. Taton
Keyword(s):  
Biochemical Characterization ◽  
Mutational Analysis ◽  
Enzyme System ◽  
Conserved Residues ◽  
Catalytic Role ◽  
Membrane Bound ◽  
Haem Iron ◽  
Oxygen Site

This report describes recent work on the process of desaturation at C5(6) of sterol precursors in plants. Biochemical characterization of the plant Δ7-sterol C5(6)-desaturase (5-DES) indicates that the enzyme system involved shows important similarities to the soluble and membrane-bound non-haem iron desaturases found in eukaryotes, including cyanide and hydrophobic chelators sensitivity, CO resistance and a requirement for exogenous reductant and molecular oxygen. Site-directed mutational analysis of highly conserved residues in 5-DES indicated that eight histidine residues from three histidine-rich motifs were essential for the catalysis, possibly by providing the ligands for a putative Fe centre. This mutational analysis also revealed the catalytic role of the functionally conserved Thr-114.

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