| 词条 | 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase |
| 释义 |
| Name = 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase | EC_number = 4.2.99.20 | CAS_number = 122007-88-9 | IUBMB_EC_number = 4/2/99/20 | GO_code = | image = | width = | caption = }}2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase, also known as SHCHC synthase, is encoded by the menH gene in E.coli and functions in the synthesis of vitamin K.[1] The specific step in the synthetic pathway that SHCHC synthase catalyzes is the conversion of 5-enolpyruvoyl-6-hydroxy-2-succinylcyclohex-3-ene-1-carboxylate to (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate and pyruvate.[2] BackgroundVitamin K is a fat soluble vitamin known to aid in blood clotting. It is recommended that all newborns receive an injection of vitamin K in order to prevent excessive bleeding of the brain after birth. There are two major forms of vitamin K that occur naturally. Phylloquinone, also known as K1, is synthesized by plants and is the major form of vitamin K in the diet. Menaquinone, K2, includes a range of forms that are synthesized by bacteria in the gut.[3]Vitamin K is synthesized from the molecule chorismate in a nine step conversion process. SHCHC synthase catalyzes the third step in the process.[4] ChemistryReaction schemeEnzyme StructureEnergetic analysis shows that SHCHC synthase has a low energetic burden for catalytic activity.[1] This means the enzyme is more prone to mutation and is one of the most diverse enzymes in the vitamin K synthetic pathway.[7] Only fifteen amino acid residues are absolutely conserved across mutations of the enzyme.[7] Catalytic MechanismThe active site contains a catalytic triad of syrine, histine and arginine, which is conserved across all mutants and is proposed to initiate the reaction.[1] The triad residues are located at Ser86, Asp210, and His232.[5] This triad is proposed to catalyze a proton extraction which triggers a transfer of electrons leading to the elimination of pyruvate and formation of SHCHC.[6] Originally, it was proposed that the transition state was stabilized by a nontraditional oxyanion hole. Now a traditional oxyanion hole is favored, but not definitive.[5] Reaction MechanismCofactors and Alternate ReactionsSHCHC synthase is unaffected by traditional cofactors such as divalent metal ions and EDTA.[1] The enzyme is fairly specific and only acts on SEPHCHC and close derivatives.[2] ControversyMenH (SHCHC synthase) was previously thought to be a thioesterase involved in hydrolyzing DHNA-CoA in a later step of menaquinone synthesis. In 2008, it was determined that MenH has poor catalytic activity toward palmitoyl-CoA, casting doubt on its role as a thioesterase.[1] Direct analysis confirmed that MenH is unable to hydrolyze DHNA-CoA.[1] In 2009, it was proposed that a dedicated hotdog fold thioesterase would be needed to catalyze the hydrolysis of DHNA-CoA.[8] A protein was identified in 2013 that could fit this role.[9] References1. ^1 2 3 4 5 {{cite journal | vauthors = Jiang M, Chen X, Guo ZF, Cao Y, Chen M, Guo Z | title = Identification and characterization of (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase in the menaquinone biosynthesis of Escherichia coli | journal = Biochemistry | volume = 47 | issue = 11 | pages = 3426–34 | date = March 2008 | pmid = | doi = 10.1021/bi7023755 }} {{Carbon-oxygen lyases}}{{Enzymes}}{{Portal bar|Molecular and Cellular Biology|border=no}}2. ^1 {{Cite web|url = http://www.brenda-enzymes.org/enzyme.php?ecno=4.2.99.20|title = Information on EC 4.2.99.20 - 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase|date = 2014-07-01|access-date = 2014-11-01|website = Brenda: The Comprehensive Enzyme Information System|publisher = TU Braunschwieg}} 3. ^{{Cite web|url = http://lpi.oregonstate.edu/infocenter/vitamins/vitaminK/|title = Micronutrient Information Center|date = 2014-11-30|access-date = 2014-11-30|website = |publisher = Linus Pauling Institute}} 4. ^van Oostende C, Widhalm JR, Furt F, Ducluzeau AL, Basset GJC (2011) Phylloquinone (Vitamin K1): function, enzymes and genes. in Advances in Botanical Research, eds Fabrice Rébeillé and Roland Douce, 59: 229-61, Academic Press (Amsterdam). 5. ^1 2 3 {{PDB|4GDM}}; {{cite journal | vauthors = Johnston JM, Jiang M, Guo Z, Baker EN | title = Crystal structures of E. coli native MenH and two active site mutants | journal = PLOS One | volume = 8 | issue = 4 | pages = e61325 | date = 2013-04-18 | pmid = 23637813 | pmc = 3630204 | doi = 10.1371/journal.pone.0061325 }} 6. ^1 {{cite journal | vauthors = Sun Y, Yin S, Feng Y, Li J, Zhou J, Liu C, Zhu G, Guo Z | title = Molecular basis of the general base catalysis of an α/β-hydrolase catalytic triad | journal = The Journal of Biological Chemistry | volume = 289 | issue = 22 | pages = 15867–79 | date = May 2014 | pmid = 24737327 | pmc = 4140940 | doi = 10.1074/jbc.M113.535641 }} 7. ^1 {{cite journal | vauthors = Jiang M, Chen X, Wu XH, Chen M, Wu YD, Guo Z | title = Catalytic mechanism of SHCHC synthase in the menaquinone biosynthesis of Escherichia coli: identification and mutational analysis of the active site residues | journal = Biochemistry | volume = 48 | issue = 29 | pages = 6921–31 | date = July 2009 | pmid = 19545176 | doi = 10.1021/bi900897h }} 8. ^{{cite journal | vauthors = Widhalm JR, van Oostende C, Furt F, Basset GJ | title = A dedicated thioesterase of the Hotdog-fold family is required for the biosynthesis of the naphthoquinone ring of vitamin K1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 14 | pages = 5599–603 | date = April 2009 | pmid = 19321747 | pmc = 2660889 | doi = 10.1073/pnas.0900738106 | url = http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1033&context=plantscifacpub }} 9. ^{{cite journal | vauthors = Chen M, Ma X, Chen X, Jiang M, Song H, Guo Z | title = Identification of a hotdog fold thioesterase involved in the biosynthesis of menaquinone in Escherichia coli | journal = Journal of Bacteriology | volume = 195 | issue = 12 | pages = 2768–75 | date = June 2013 | pmid = 23564174 | pmc = 3697248 | doi = 10.1128/JB.00141-13 }} 2 : EC 4.2.99|Enzymes of known structure |
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