Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: System in biology leading to cell pathology: stable proteinprotein interactions after covalent modifications by small molecules or in transgenic cells
The food we eat has a major effect on our physical health and psychological wellbeing.
An understanding of the way in which nutrients are metabolized, and hence of the
principles of biochemistry, is essential for an understanding of the scientific basis of
what we would call a prudent or healthy diet.
My aim in the following pages is to explain both the conclusions of the many
expert committees that have deliberated on the problems of nutritional requirements,
diet and health over the years and also the scientific basis on which these experts have
reached their conclusions.
Ammonium assimilation is tightly regulated in nitrogen-fixing bacteria; the
target of regulation is primarily the activity of the key enzyme glutamine
synthetase that is regulated by reversible covalent modification by AMP
groups in reactions catalysed by the bifunctional adenylyltransferase
(ATase). The properties and regulation of ATase fromEscherichia colihave
been studied in great detail.
The building blocks of most signal transduction pathways are pairs of
enzymes, such as kinases and phosphatases, that control the activity of pro-tein targets by covalent modification. It has previously been shown [Gold-beter A & Koshland DE (1981)Proc Natl Acad Sci USA78, 6840–6844]
that these systems can be highly sensitive to changes in stimuli if their cata-lysing enzymes are saturated with their target protein substrates.
Covalent modifications of proteins often modulate their biological func-tions or change their subcellular location. Among the many known protein
modifications, three are exceptional in that they only occur on single pro-teins: ethanolamine phosphoglycerol, diphthamide and hypusine.
The fourth lysine of histone H3 is post-translationally modified by a methyl
group via the action of histone methyltransferase, and such a covalent
modification is associated with transcriptionally active and⁄or repressed
chromatin states. Thus, histone H3 lysine 4 methylation has a crucial role
in maintaining normal cellular functions.
Previous studies have suggested that positive feedback loops and ultrasensi-tivity are prerequisites for bistability in covalent modification cascades.
However, it was recently shown that bistability and hysteresis can also arise
solely from multisite phosphorylation.
A detailed comparison between native chlorite dismutase
from Ideonella dechloratans, and the recombinant version
of the protein produced inEscherichia coli, suggests the
presence of a covalent modification in the native enzyme.
Although the native and recombinant N- and C-terminal
sequences are identical, the enzymes display different
electrophoretic mobilities, and produce different peptide
maps upon digestion with trypsin and separation of
fragments using capillary electrophoresis.
The following will be discussed in this chapter: Allosteric regulation, covalent modification, regulation of enzyme activity by subunit association/disassociation, regulation by proteolytic cleavage of proenzyme.
2-Cys peroxiredoxins are peroxidases devoid of prosthetic groups that
mediate in the defence against oxidative stress and the peroxide activation
of signaling pathways. This dual capacity relies on the high reactivity of
the conserved peroxidatic and resolving cysteines, whose modification
embraces not only the usual thiol–disulfide exchange but also higher oxida-tion states of the sulfur atom.
Nitrogenase Fe-protein modification was analyzed in the endophyticb-pro-teobacterium Azoarcussp. BH72. Application of modern MS techniques
localized the modification in the peptide sequence and revealed it to be an
ADP-ribosylation on Arg102 of one subunit of nitrogenase Fe-protein.
Interaction of cytokines with their cognate receptors leads
to the activation of latent transcription factors, the signal
transducer and activator of transcription (STAT) proteins.
Numerous studies have identified the critical roles played
by STAT proteins in regulating cell proliferation, differ-entiation and survival. Consequently, the activity of STAT
proteins is negatively regulated by a variety of different
mechanisms, which include alternative splicing, covalent
modifications, protein–protein interactions with negative
regulatory proteins and proteolytic processing by pro-teases....
Ammonium assimilation inEscherichia coliis regulated through multiple
mechanisms (metabolic, signal transduction leading to covalent modification,
transcription, and translation), which (in-)directly affect the activities of its
two ammonium-assimilating enzymes, i.e. glutamine synthetase (GS) and
glutamate dehydrogenase (GDH).
Mitochondrial cytochromescandc1 are present in all eukaryotes that use
oxygen as the terminal electron acceptor in the respiratory chain. Matura-tion of c-type cytochromes requires covalent attachment of the heme cofac-tor to the protein, and there are at least five distinct biogenesis systems
that catalyze this post-translational modification in different organisms and
Sumoylation is a multi-step protein modification reaction in which SUMO
(small ubiquitin-like modifier) proteins are covalently attached to lysine res-idues of substrate proteins. Here, we compare the sequences and structures
of modifiers and enzymes involved in sumoylation with those of the related
ubiquitination and neddylation cascades.
O-Fucosylation is a post-translational glycosylation in which anO-fucose
is covalently attached to the hydroxyl group of a specific serine or threon-ine residue. This modification occurs within the consensus sequence
C2X4)5(S⁄T)C3 present on epidermal growth factor-like repeats of several
proteins, including the Notch receptors and their ligands.
Sumoylation is a post-translational modification system that covalently
attaches the small ubiquitin-related modifier (SUMO) to target proteins.
Ubc9 is required as the E2-type enzyme for SUMO-1 conjugation to tar-gets. Here, we show that Ubc9 interacts with the meiosis-specific RecA
homolog, Lim15⁄Dmc1 in the basidiomyceteCoprinus cinereus(CcLim15),
and mediates sumoylation of CcLim15 during meiosis.
Folding of DNA into chromatin is mediated by binding to
histones such as H4; association of DNA with histones is
regulated by covalent histone modifications,e.g. acetylation,
methylation,andbiotinylation.We sought to identifyamino-acid residues that are biotinylated in histone H4,and to
determine whether acetylation and methylation of histones
affect biotinylation. Synthetic peptides spanning fragments
of human histone H4 were biotinylated enzymatically using
biotinidase. Peptide-bound biotin was probed with strept-avidin–peroxidase....
Functional protein serotonylation is a newly recognized post-translational
modification with the primary biogenic monoamine (PBMA) serotonin
(5-HT). This covalent protein modification is catalyzed by transglutaminas-es (TGs) and, for example, acts in the constitutive activation of small GTP-ases.
Proteins are covalently modified with a variety of lipids, including fatty
acids, isoprenoids, and cholesterol. Lipid modifications play important
roles in the localization and function of proteins. The focus of this review
is S-palmitoylation, the reversible addition of palmitate and other long-chain fatty acids to proteins at cysteine residues in a variety of sequence