Naphthoate synthase
{{redirects here|MenB|the meningococcal B vaccine|Meningococcal vaccine}}
{{infobox enzyme
| Name = 1,4-dihydroxy-2-naphthoyl-CoA synthase
| EC_number = 4.1.3.36
| CAS_number = 72506-71-9
| GO_code = 0008935
| image = 4qii.jpg
| width = 270
| caption = 1,4-Dihydroxy-2-naphthoyl-CoA synthase hexamer, Mycobacterium tuberculosis
}}The enzyme 1,4-dihydroxy-2-naphthoyl-CoA synthase ({{EnzExplorer|4.1.3.36}}) catalyzes the sixth step in the biosynthesis of phylloquinone and menaquinone, the two forms of vitamin K. In E. coli, 1,4-dihydroxy-2-naphthoyl-CoA synthase, formerly known as naphthoate synthase, is encoded by menB and uses O-succinylbenzoyl-CoA as a substrate and converts it to 1,4-dihydroxy-2-naphthoyl-CoA.
Nomenclature
MenB is part of the crotonase fold super family, named after the crotonase fold in their structure.{{Cite journal|title = Structural Basis of the Induced-Fit Mechanism of 1,4-Dihydroxy-2-Naphthoyl Coenzyme A Synthase from the Crotonase Fold Superfamily|date = April 26, 2013|pmc=3637252 | pmid=23658663|doi=10.1371/journal.pone.0063095|volume=8|journal=PLOS ONE|pages=e63095|vauthors=Sun Y, Song H, Li J, Li Y, Jiang M, Zhou J, Guo Z|issue = 4|bibcode = 2013PLoSO...863095S|doi-access = free}} The systematic name for MenB is 4-(2-carboxyphenyl)-4-oxobutanoyl-CoA dehydratase (cyclizing).{{Cite web|url = http://www.brenda-enzymes.info/enzyme.php?ecno=4.1.3.36|title = Information on EC 4.1.3.36 - 1,4-dihydroxy-2-naphthoyl-CoA synthase|date = July 2014|access-date = December 2, 2014|website = BRENDA}} Other common names include:
- Naphthoate synthase
- 1,4-dihydroxy-2-naphthoate synthase
- Dihydroxynaphthoate synthase
- DHNA-CoA synthase
Reaction
File:Updated catalyzed reaction of MenB.png{{Cite journal |vauthors=van Oostende C, Widhalm JR, Furt F, Ducluzeau AL, ((Basset GJC)) |date=2011 |title=Phylloquinone (Vitamin K1): function, enzymes and genes |journal=Advances in Botanical Research |editor=Fabrice Rébeillé |editor2=Roland Douce|editor2-link=Roland Douce |volume=59 |pages=229–61 |publisher=Academic Press |location=Amsterdam |doi = 10.1016/B978-0-12-385853-5.00001-5 }}
It was originally thought that the product of this reaction had an oxygen where the SCoA currently resides, however; new research has shown that MenB only catalyzes the above reaction. There is a different enzyme that cleaves the SCoA and attaches the oxygen.
Structure
File:Cartoon structure of MenB.pngMenB is composed of two hexamers in an asymmetric unit, these hexamers are each composed of two trimers in an eclipsed arrangement. Each sub unit of the hexamers has three C terminal alpha helices, and a N terminal spiral core. These sub units come together to form the active site of the enzyme.
The channel formed by alpha helices that can be seen in the middle of the enzyme leads to the active site. This opening exists on both top and bottom of the enzyme, allowing substrates different entry points to the active site, which rests in the middle of the enzyme.
Six different crystal structures have been studied for MenB in Escherichia coli their PDB codes are: [http://www.rcsb.org/pdb/explore/explore.do?job=summary&pdbId=3t88 3t88], [http://www.rcsb.org/pdb/explore/explore.do?job=summary&pdbId=3t89 3t89], [http://www.rcsb.org/pdb/explore/explore.do?job=summary&pdbId=4els 4els], [http://www.rcsb.org/pdb/explore/explore.do?job=summary&pdbId=4elw 4elw], [http://www.rcsb.org/pdb/explore/explore.do?job=summary&pdbId=4elx 4elx], and [http://www.rcsb.org/pdb/explore/explore.do?job=summary&pdbId=4i42 4i42].
Other structures have been solved for this class of enzymes, with PDB accession codes {{PDB link|1Q51}}, {{PDB link|1Q52}}, {{PDB link|1RJM}}, {{PDB link|1RJN}}, and {{PDB link|2IEX}}.
Homologs
Homologous genes MenB exist in many different organisms, such as; Galium mollugo, Geobacillus kaustophilus, Mycobacterium phlei, Mycobacterium tuberculosis, Spinacia oleracea, and Staphylococcus aureus.
MenB is only found in biosynthesis pathways in plants and bacteria, it does not exist in any other organisms. However, mammals require vitamin K in their diet because it is vital in the blood clotting process.
Cofactors/Inhibitors
MenB does not require any cofactors to catalyze the reaction.
In the organism Escherichia coli three inhibitors exist: 1-hydroxy-2-naphthoyl-CoA, [http://www.brenda-enzymes.info/structure.php?n=283036 2,3-dihydroxybenzoyl-CoA], and [http://www.brenda-enzymes.info/structure.php?n=283037 2,4-dihydroxybenzoyl-CoA].
References
{{reflist|1}}
- {{cite journal |vauthors=Kolkmann R, Leistner E | date = 1987 | title = 4-(2'-Carboxyphenyl)-4-oxobutyryl coenzyme A ester, an intermediate in vitamin K2 (menaquinone) biosynthesis | journal = Z. Naturforsch. C | volume = 42 | pages = 1207–14 | pmid = 2966501 | issue = 11–12 | doi=10.1515/znc-1987-11-1212| s2cid = 41701934 | doi-access = free }}
- {{cite journal |vauthors=Meganathan R, Bentley R | date = 1979 | title = Menaquinone (vitamin K2) biosynthesis: conversion of o-succinylbenzoic acid to 1,4-dihydroxy-2-naphthoic acid by Mycobacterium phlei enzymes | journal = J. Bacteriol. | volume = 140 | pages = 92–8 | pmid = 500558 | issue = 1 | doi = 10.1128/JB.140.1.92-98.1979 | pmc = 216783 }}
{{Carbon-carbon lyases}}
{{Enzymes}}
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