Leukotriene C4 synthase
From Proteopedia
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Leukotriene C<sub>4</sub> synthase is a unique membrane-bound enzyme that catalyzes the committed step in the biosynthesis of all the peptidoleukotrienes, also known as <b>cysteinyl leukotrienes</b> because of the presence of [http://en.wikipedia.org/wiki/cysteine cysteine] in their structures. The cysteinyl leukotrienes make up the slow-reacting substance of anaphylaxis ([http://en.wikipedia.org/wiki/SRS-A SRS-A]). | Leukotriene C<sub>4</sub> synthase is a unique membrane-bound enzyme that catalyzes the committed step in the biosynthesis of all the peptidoleukotrienes, also known as <b>cysteinyl leukotrienes</b> because of the presence of [http://en.wikipedia.org/wiki/cysteine cysteine] in their structures. The cysteinyl leukotrienes make up the slow-reacting substance of anaphylaxis ([http://en.wikipedia.org/wiki/SRS-A SRS-A]). | ||
| - | Specifically, LTC<sub>4</sub>S conjugates reduced glutathione with the unstable epoxide LTA<sub>4</sub> to form LTC<sub>4</sub>, making it a member of the glutathione <i>S</i>-transferase multigene family. Unlike other members of this family, however, LTC<sub>4</sub>S is not involved in cellular detoxification at all, and instead seems to be exclusively committed to the biosynthesis of LTC<sub>4</sub>.<ref>PMID:1517222</ref> | + | Specifically, LTC<sub>4</sub>S conjugates reduced glutathione with the unstable epoxide LTA<sub>4</sub> to form LTC<sub>4</sub>, making it a member of the glutathione <i>S</i>-transferase multigene family. Unlike other members of this family, however, LTC<sub>4</sub>S is not involved in cellular detoxification at all, and instead seems to be exclusively committed to the biosynthesis of LTC<sub>4</sub>.<ref>PMID:1517222</ref> <scene name='43/433642/Cv/6'>Active site</scene>. Water molecules shown as red spheres. |
==Relevance== | ==Relevance== | ||
Revision as of 12:30, 13 April 2016
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3D Structures of Leukotriene C4 synthase
Updated on 13-April-2016
2pno, 2uui, 3pcv – hLC4S - human
4nta – mLC4S - mouse
4ntb, 4ntf - mLC4S + glutathione derivative
3leo – hLC4S (mutant)+glutathione
3hkk, 2uuh - hLC4S +glutathione
3b29 – hLC4S + dodecyl-β-D-selenomaltoside
4j7t, 4j7y, 4jcz, 4jrz – hLC4S + product analog
4jc7 – hLC4S (mutant) + product analog
References
- ↑ Lam BK, Penrose JF, Freeman GJ, Austen KF. Expression cloning of a cDNA for human leukotriene C4 synthase, an integral membrane protein conjugating reduced glutathione to leukotriene A4. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7663-7. PMID:8052639
- ↑ Penrose JF, Spector J, Baldasaro M, Xu K, Boyce J, Arm JP, Austen KF, Lam BK. Molecular cloning of the gene for human leukotriene C4 synthase. Organization, nucleotide sequence, and chromosomal localization to 5q35. J Biol Chem. 1996 May 10;271(19):11356-61. PMID:8626689
- ↑ Nicholson DW, Ali A, Klemba MW, Munday NA, Zamboni RJ, Ford-Hutchinson AW. Human leukotriene C4 synthase expression in dimethyl sulfoxide-differentiated U937 cells. J Biol Chem. 1992 Sep 5;267(25):17849-57. PMID:1517222
- ↑ Welsch DJ, Creely DP, Hauser SD, Mathis KJ, Krivi GG, Isakson PC. Molecular cloning and expression of human leukotriene-C4 synthase. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9745-9. PMID:7937884
- ↑ Lam BK, Penrose JF, Freeman GJ, Austen KF. Expression cloning of a cDNA for human leukotriene C4 synthase, an integral membrane protein conjugating reduced glutathione to leukotriene A4. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7663-7. PMID:8052639
- ↑ Martinez Molina D, Wetterholm A, Kohl A, McCarthy AA, Niegowski D, Ohlson E, Hammarberg T, Eshaghi S, Haeggstrom JZ, Nordlund P. Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase. Nature. 2007 Aug 2;448(7153):613-6. Epub 2007 Jul 15. PMID:17632546 doi:10.1038/nature06009
- Created with the participation of Shilpa Nadimpalli.
