WordNet
- limit, block, or decrease the action or function of; "inhibit the action of the enzyme"; "inhibit the rate of a chemical reaction"
- control and refrain from showing; of emotions, desires, impulses, or behavior (同)bottle up, suppress
- limit the range or extent of; "Contact between the young was inhibited by strict social customs"
- the process of producing a chemical compound (usually by the union of simpler chemical compounds)
- the combination of ideas into a complex whole (同)synthetic thinking
- any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"
- a substance that retards or stops an activity
PrepTutorEJDIC
- 〈感情・欲望・行動・作用など〉‘を'抑制する / (…しないように)〈人〉‘を'抑制する,妨げる《+『名』+『from』+『名』(do『ing』)》
- 〈U〉総合,統合[すること] / 〈C〉総合体,統合されたもの / 〈U〉合成
- 蛋白(たんばく)質
- 抑制する人(物) / 化学反応抑制剤
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/09/06 02:48:25」(JST)
[Wiki en表示]
Simplified schematic of mRNA translation
A protein synthesis inhibitor is a substance that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins.[1]
While a broad interpretation of this definition could be used to describe nearly any antibiotic, in practice, it usually refers to substances that act at the ribosome level (either the ribosome itself or the translation factor),[2] taking advantages of the major differences between prokaryotic and eukaryotic ribosome structures.
Toxins such as ricin also function via protein synthesis inhibition.[3] Ricin acts at the eukaryotic 60S.[4]
Examples:
- Neomycin
- Geneticin, also called G418
Contents
- 1 Mechanism
- 1.1 Earlier stages
- 1.2 Initiation
- 1.3 Aminoacyl tRNA entry
- 1.4 Proofreading
- 1.5 Peptidyl transfer
- 1.6 Ribosomal translocation
- 1.7 Termination
- 1.8 Protein synthesis inhibitors of unspecified mechanism
- 2 Binding site
- 3 See also
- 4 References
Mechanism
In general, protein synthesis inhibitors work at different stages of prokaryotic mRNA translation into proteins, like initiation, elongation (including aminoacyl tRNA entry, proofreading, peptidyl transfer, and ribosomal translocation) and termination:
Earlier stages
- Rifamycin inhibits prokaryotic DNA transcription into mRNA by inhibiting DNA-dependent RNA polymerase by binding its beta-subunit.
Initiation
- Linezolid acts at the initiation stage,[5] probably by preventing the formation of the initiation complex, although the mechanism is not fully understood.[6]
Aminoacyl tRNA entry
- Tetracyclines and Tigecycline[7] (a glycylcycline related to tetracyclines) block the A site on the ribosome, preventing the binding of aminoacyl tRNAs.
Proofreading
- Aminoglycosides, among other potential mechanisms of action, interfere with the proofreading process, causing increased rate of error in synthesis with premature termination.[8]
Peptidyl transfer
- Chloramphenicol blocks the peptidyl transfer step of elongation on the 50S ribosomal subunit in both bacteria and mitochondria.
- Macrolides (as well as inhibiting ribosomal translocation[9] and other potential mechanisms) bind to the 50s ribosomal subunits, inhibiting peptidyl transfer.
- Quinupristin/dalfopristin act synergistically, with dalfopristin, enhancing the binding of quinupristin, as well as inhibiting peptidyl transfer.[10] Quinupristin binds to a nearby site on the 50S ribosomal subunit and prevents elongation of the polypeptide,[10] as well as causing incomplete chains to be released.[10]
Ribosomal translocation
- Macrolides,[9] clindamycin[11] and aminoglycosides[8] (with all these three having other potential mechanisms of action as well), have evidence of inhibition of ribosomal translocation.
- Fusidic acid prevents the turnover of elongation factor G (EF-G) from the ribosome.
Termination
- Macrolides[12][13] and clindamycin[12][13] (both also having other potential mechanisms) cause premature dissociation of the peptidyl-tRNA from the ribosome.
- Puromycin has a structure similar to that of the tyrosinyl aminoacyl-tRNA. Thus, it binds to the ribosomal A site and participates in peptide bond formation, producing peptidyl-puromycin. However, it does not engage in translocation and quickly dissociates from the ribosome, causing a premature termination of polypeptide synthesis.
- Streptogramins also cause premature release of the peptide chain.[14]
Protein synthesis inhibitors of unspecified mechanism
- Retapamulin[15]
- Mupirocin
- Fusidic acid
Binding site
The following antibiotics bind to the 30S subunit of the ribosome:
- Aminoglycosides [14]
- Tetracyclines[14]
The following antibiotics bind to the 50S ribosomal subunit:
- Chloramphenicol[14]
- Erythromycin[14]
- Clindamycin[14]
- Linezolid[14] (an oxazolidinone)
- Telithromycin[14]
- Streptogramins[14]
- Retapamulin[15]
See also
- Protein biosynthesis
- Prokaryotic translation
References
- ^ "Definition: protein synthesis inhibitor from Online Medical Dictionary".
- ^ "7.344 Antibiotics, Toxins, and Protein Engineering, Spring 2007". MIT OpenCourseWare.
- ^ Leonard JE, Grothaus CD, Taetle R (October 1988). "Ricin binding and protein synthesis inhibition in human hematopoietic cell lines". Blood. 72 (4): 1357–1363. PMID 3167211.
- ^ Terao K, Uchiumi T, Endo Y, Ogata K (June 1988). "Ricin and alpha-sarcin alter the conformation of 60S ribosomal subunits at neighboring but different sites". Eur. J. Biochem. 174 (3): 459–463. doi:10.1111/j.1432-1033.1988.tb14120.x. PMID 3391162.
- ^ Swaney SM, Aoki H, Ganoza MC, Shinabarger DL (December 1998). "The Oxazolidinone Linezolid Inhibits Initiation of Protein Synthesis in Bacteria". Antimicrob. Agents Chemother. 42 (12): 3251–3255. PMC 106030. PMID 9835522.
- ^ Skripkin E, McConnell TS, DeVito J, et al. (October 2008). "Rχ-01, a New Family of Oxazolidinones That Overcome Ribosome-Based Linezolid Resistance". Antimicrobial Agents and Chemotherapy. 52 (10): 3550–3557. doi:10.1128/AAC.01193-07. PMC 2565890. PMID 18663023.
- ^ Slover CM, Rodvold KA, Danziger LH (June 2007). "Tigecycline: a novel broad-spectrum antimicrobial". Ann Pharmacother. 41 (6): 965–972. doi:10.1345/aph.1H543. PMID 17519296. Retrieved 2009-12-19.
- ^ a b Flavio Guzmán (12/08/2008). "Protein synthesis inhibitors: aminoglycosides mechanism of action animation. Classification of agents". Pharmamotion.
- ^ a b Protein synthesis inhibitors: macrolides mechanism of action animation. Classification of agents Pharmamotion. Author: Gary Kaiser. The Community College of Baltimore County. Retrieved on July 31, 2009
- ^ a b c Page 212 in: Title: Hugo and Russell's pharmaceutical microbiology Authors: William Barry Hugo, Stephen P. Denyer, Norman A. Hodges, Sean P. Gorman Edition: 7, illustrated Publisher: Wiley-Blackwell, 2004 ISBN 0-632-06467-6 Length: 481 pages
- ^ Wisteria Lane cases --> CLINDAMYCIN University of Michigan. Retrieved on July 31, 2009
- ^ a b Menninger JR (1995). "Mechanism of inhibition of protein synthesis by macrolide and lincosamide antibiotics". J Basic Clin Physiol Pharmacol. 6 (3–4): 229–250. doi:10.1515/JBCPP.1995.6.3-4.229. PMID 8852269.
- ^ a b Tenson T, Lovmar M, Ehrenberg M (July 2003). "The mechanism of action of macrolides, lincosamides and streptogramin B reveals the nascent peptide exit path in the ribosome". J. Mol. Biol. 330 (5): 1005–1014. doi:10.1016/S0022-2836(03)00662-4. PMID 12860123.
- ^ a b c d e f g h i Levinson, Warren (2008). Review of medical microbiology and immunology. New York: McGraw-Hill Medical. ISBN 978-0-07-149620-9.
- ^ a b Drugbank.ca > Showing drug card for Retapamulin (DB01256) Update Date: 2009-06-23
|
Antibacterials: protein synthesis inhibitors (J01A, J01B, J01F, J01G, QJ01XQ)
|
|
| 30S |
Aminoglycosides
(initiation inhibitors) |
| -mycin (Streptomyces) |
- Streptomycin#
- Dihydrostreptomycin
- Neomycin#
- Framycetin
- Paromomycin
- Ribostamycin
- Kanamycin#
- Amikacin
- Arbekacin
- Bekanamycin
- Dibekacin
- Tobramycin
- Spectinomycin#
- Hygromycin B
|
|
| -micin (Micromonospora) |
- Gentamicin#
- Netilmicin
- Sisomicin
- Plazomicin†
- Isepamicin
|
|
|
Tetracycline antibiotics
(tRNA binding) |
| Tetracyclines |
- Doxycycline#
- Chlortetracycline
- Clomocycline
- Demeclocycline
- Lymecycline
- Meclocycline
- Metacycline
- Minocycline
- Oxytetracycline
- Penimepicycline
- Rolitetracycline
- Tetracycline
|
|
| Glycylcyclines |
|
|
|
|
| 50S |
Oxazolidinone
(initiation inhibitors) |
- Eperezolid
- Linezolid
- Posizolid
- Radezolid
- Ranbezolid
- Sutezolid
- Tedizolid
|
|
| Peptidyl transferase |
| Amphenicols |
- Chloramphenicol#
- Azidamfenicol
- Thiamphenicol
- Florfenicol
|
|
| Pleuromutilins |
- Retapamulin
- Tiamulin
- Valnemulin
|
|
|
| MLS (transpeptidation/translocation) |
| Macrolides |
- Azithromycin#
- Clarithromycin
- Dirithromycin
- Erythromycin#
- Flurithromycin
- Josamycin
- Midecamycin
- Miocamycin
- Oleandomycin
- Rokitamycin
- Roxithromycin
- Spiramycin
- Troleandomycin
- Tylosin
- Ketolides
- Telithromycin
- Cethromycin
- Solithromycin†
|
|
| Lincosamides |
- Clindamycin#
- Lincomycin
- Pirlimycin
|
|
| Streptogramins |
- Pristinamycin
- Quinupristin/dalfopristin
- Virginiamycin
|
|
|
|
| EF-G |
|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- MG132 Induces Expression of Monocyte Chemotactic Protein-Induced Protein 1 in Vascular Smooth Muscle Cells.
- Tan X1,2, Gao J3, Shi Z1, Tai S1, Chan LL1, Yang Y4, Peng DQ4, Liao DF2, Jiang ZS1,5, Chang YZ6, Gui Y3, Zheng XL7.
- Journal of cellular physiology.J Cell Physiol.2017 Jan;232(1):122-8. doi: 10.1002/jcp.25396. Epub 2016 Apr 14.
- Monocyte chemoattractant protein-1 (MCP-1) has been reported to induce the expression of monocyte chemotactic protein-induced protein 1 (MCPIP1), which undergoes ubiquitination degradation. Therefore, we predict that in vascular smooth muscle (VSMCs), MCPIP1 may be induced by MCP-1 and undergo degra
- PMID 27035356
- Macrocyclization and labeling of helix-loop-helix peptide with intramolecular bis-thioether linkage.
- Nishihara T1, Kitada H1, Fujiwara D1, Fujii I1.
- Biopolymers.Biopolymers.2016 Nov 4;106(4):415-21. doi: 10.1002/bip.22826.
- Conformationally constrained peptides have been developed as an inhibitor for protein-protein interactions (PPIs), and we have de novo designed cyclized helix-loop-helix (cHLH) peptide with a disulfide bond consisting of 40 amino acids to generate molecular-targeting peptides. However, synthesis of
- PMID 26917088
- The inhibitory effect of dehydroepiandrosterone and its derivatives against influenza A virus in vitro and in vivo.
- Yang Q1, Mao Q2, Liu M1, Wang K1, Wu Z1, Fang W1, Yang Z1, Luo P2,3, Ke S4, Shi L5,6.
- Archives of virology.Arch Virol.2016 Nov;161(11):3061-72. doi: 10.1007/s00705-016-2993-6. Epub 2016 Aug 12.
- The antiviral activity of dehydroepiandrosterone (DHEA) and 21 synthetic derivatives against influenza A virus (IAV) replication was investigated in vitro in cell culture. Our results revealed that three DHEA analogues were potent inhibitors of IAV multiplication in MDCK cells and mainly blocked the
- PMID 27518401
Japanese Journal
- Synthesis and Characterization of 8-Nitroguanosine 3',5'-Cyclic Monophosphorothioate Rp-Isomer as a Potent Inhibitor of Protein Kinase G1α
- TSC2/Rheb signaling mediates ERK-dependent regulation of mTORC1 activity in C2C12 myoblasts
- Differential requirements of hippocampal de novo protein and mRNA synthesis in two long-term spatial memory tests: Spontaneous place recognition and delay-interposed radial maze performance in rats
Related Links
- To date, the effects of protein synthesis inhibitors (PSI) in learning and memory processes have been attributed to translational arrest and consequent inhibition of de novo protein synthesis. Here we argue that amnesia ...
- Gm+ (**strep pyogenes, Strep pneumo, S. viridans, S. aureus, Listeria Gm- Pertussus, Legionella, N.gonorrhea, mycobacterium. Food poisoning: Campylybacter ... ***MAO inhibitor - caution w sympathomimetic and dopaminergics ...
Related Pictures
★リンクテーブル★
[★]
- 英
- protein synthesis inhibitor, inhibitor of protein synthesis
- 同
- タンパク合成阻害剤、タンパク質合成阻害剤、タンパク質合成阻害薬
[★]
- 英
- protein synthesis inhibitor
- 関
- タンパク合成阻害薬、タンパク合成阻害剤、タンパク質合成阻害薬
[★]
- 英
- protein synthesis inhibitor
- 関
- タンパク合成阻害薬、タンパク合成阻害剤、タンパク質合成阻害剤
[★]
- 関
- abrogate、block、depress、depression、deter、inhibition、interdict、prevent、prevention、repress、repression、restrain、restraint、suppress、suppression
[★]
- 総合、統合、組み立て(opp.analysis。総合体、統合体。(化)合成、人造。(外科)接骨、復位。
- 関
- construction、elaboration、syntheses、synthesize、synthetic
[★]
- 関
- blocker、depressant、suppressant