# Lactacystin
> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Lactacystin
> Markdown URL: https://mediated.wiki/source/Lactacystin.md
> Source: https://en.wikipedia.org/wiki/Lactacystin
> Source revision: 1215726961
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)
{{Chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 400128403
| ImageFile = Lactacystin.svg
| ImageFile_Ref = {{chemboximage|correct|??}}
| ImageSize = 244
| ImageName = Stereo skeletal formula of lactacystin ((2''R'')-2-amid, (2''R'',3''S'',4''R'')-3-hydrox,-2-((1''S'')-1-hydrox)prop,-4-meth)
| SystematicName = (2''R'')-2-Acetamido-3-({(2''R'',3''S'',4''R'')-3-hydroxy-2-[(1''S'')-1-hydroxy-2-methylpropyl]-4-methyl-5-oxopyrrolidine-2-carbonyl}sulfanyl)propanoic acid
|Section1={{Chembox Identifiers
| CASNo = 133343-34-7
| CASNo_Ref = {{cascite|correct|??}}
| PubChem = 3870
| PubChem1 =
| PubChem1_Comment = -2-((1''S'')-1-hydrox)prop
| PubChem2 = 45039639
| PubChem2_Comment = (3''S'',4''R'')-3-hydrox,-2-((1''R'')-1-hydrox)prop,-4-meth
| PubChem3 = 46782036
| PubChem3_Comment = (2''R'')-2-amid, (3''S'',4''R'')-3-hydrox,-2-((1''R'')-1-hydrox)prop,-4-meth
| PubChem4 = 3034764
| PubChem4_Comment = (2''R'')-2-amid, (3''S'',4''R'')-3-hydrox,-2-((1''S'')-1-hydrox)prop,-4-meth
| ChemSpiderID = 3735
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID1 = 2299173
| ChemSpiderID1_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID1_Comment = (2''R'')-2-amid, (3''S'',4''R'')-3-hydrox,-2-((1''S'')-1-hydrox)prop,-4-meth
| MeSHName = Lactacystin
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 52722
| ChEMBL = 374308
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| SMILES = CC(C)C(O)C1(NC(=O)C(C)C1O)C(=O)SCC(NC(C)=O)C(O)=O
| SMILES1 = CC(=O)NC(CSC(=O)C1(C(O)C(C)C)NC(=O)C(C)C1O)C(=O)O
| SMILES2 = OC1C(C)C(=O)NC1(C(=O)SCC(NC(C)=O)C(O)=O)C(O)C(C)C
| StdInChI = 1S/C15H24N2O7S/c1-6(2)10(19)15(11(20)7(3)12(21)17-15)14(24)25-5-9(13(22)23)16-8(4)18/h6-7,9-11,19-20H,5H2,1-4H3,(H,16,18)(H,17,21)(H,22,23)
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| InChI = 1/C15H24N2O7S/c1-6(2)10(19)15(11(20)7(3)12(21)17-15)14(24)25-5-9(13(22)23)16-8(4)18/h6-7,9-11,19-20H,5H2,1-4H3,(H,16,18)(H,17,21)(H,22,23)
| StdInChIKey = DAQAKHDKYAWHCG-UHFFFAOYSA-N
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| InChIKey = DAQAKHDKYAWHCG-WBMULXAQBF
}}
|Section2={{Chembox Properties
| C=15 | H=24 | N=2 | O=7 | S=1
| LogP = 0.086
| pKa = 3.106
| pKb = 10.891
}}
}}
'''Lactacystin''' is an [organic compound](/source/organic_compound) naturally [synthesized](/source/organic_synthesis) by [bacteria](/source/bacteria) of the [genus](/source/genus) ''[Streptomyces](/source/Streptomyces)'' first identified as an inducer of neuritogenesis in neuroblastoma cells in 1991.[Omura S, Fujimoto T, Otoguro K, Matsuzaki K, Moriguchi R, Tanaka H, Sasaki Y. (1991). Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells: S. Omura, et al. ''J. Antibiot.'' 44(1):113-6.] The target of lactacystin was subsequently found to be the [proteasome](/source/proteasome) on the basis of its affinity for certain catalytic subunits of the proteasome by Fenteany and co-workers in 1995.[{{cite journal |vauthors=Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL |title=Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin |journal=Science |volume=268 |issue=5211 |pages=726–31 |year=1995 |pmid=7732382 |doi=10.1126/science.7732382|bibcode=1995Sci...268..726F |s2cid=37779687 }}] The proteasome is a protein complex responsible for the bulk of proteolysis in the cell, as well as proteolytic activation of certain protein substrates. Lactacystin was the first non-peptidic proteasome inhibitor discovered and is widely used as a research tool in biochemistry and cell biology. The transformation product of lactacystin clasto-lactacystin β-lactone (also known as omuralide) covalently modifies the amino-terminal threonine of specific catalytic subunits of the proteasome, a discovery that helped to establish the proteasome as a mechanistically novel class of protease: an amino-terminal [threonine protease](/source/threonine_protease). The molecule is commonly used in [biochemistry](/source/biochemistry) and [cell biology](/source/cell_biology) laboratories as a selective inhibitor of the [proteasome](/source/proteasome).[{{cite journal |vauthors=Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL |title=Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin |journal=Science |volume=268 |issue=5211 |pages=726–31 |year=1995 |pmid=7732382 |doi=10.1126/science.7732382|bibcode=1995Sci...268..726F |s2cid=37779687 }}][{{cite journal |vauthors=Fenteany G, Schreiber SL |title=Lactacystin, proteasome function, and cell fate |journal=J. Biol. Chem. |volume=273 |issue=15 |pages=8545–8 |year=1998 |pmid= 9535824 |doi=10.1074/jbc.273.15.8545|doi-access= free}}] The first [total synthesis](/source/total_synthesis) of lactacystin was developed in 1992 by Corey and Reichard,[''"Total Synthesis of Lactacystin"'' Corey, E. J.; Reichard, G. A. ''[J. Am. Chem. Soc.](/source/J._Am._Chem._Soc.)'' '''1992''', ''114'', 10677.] and a number of other syntheses of this molecule have also been published. There are more than 1,660 entries for lactacystin in [PubMed](/source/PubMed) as of January 2019.
==See also==
*[Satoshi Ōmura](/source/Satoshi_%C5%8Cmura)
==References==
{{Reflist}}
Category:Acetamides
Category:Pyrrolidones
Category:Secondary alcohols
Category:Total synthesis
Category:Lactams
---
Adapted from the Wikipedia article [Lactacystin](https://en.wikipedia.org/wiki/Lactacystin) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Lactacystin?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.