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MetaCyc Enzyme: 1,4-dihydroxy-2-naphthoyl-CoA synthase

Gene: menB Accession Numbers: EG11368 (MetaCyc), b2262, ECK2256

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of 1,4-dihydroxy-2-naphthoyl-CoA synthase = [MenB]6

Summary:
1,4-Dihydroxy-2-naphthoyl-CoA synthase catalyzes a major step in menaquinone biosynthesis, formation of the bicyclic ring system by an intramolecular Claisen condensation [Heide82, Sharma92].

The enzyme requires a bound bicarbonate ion for full activity, and the crystal structure of the Salmonella enterica ortholog contains a bicarbonate ion. Both the S. enterica and the E. coli enzymes contain a glycine residue in the position corresponding to the essential active site Asp185 residue of the Mycobacterium tuberculosis enzyme, and the bicarbonate ion is found close to this Gly156 residue. Site-directed mutagenesis showed that Gly156 is essential for catalytic activity [Jiang10]. Asp163 interacts with the C1 hydroxyl group of DHNA-CoA; a D163A mutation abolishes activity as well as ligand binding [Chen11a]. A Y97F mutant lacks catalytic activity [Li11]. Reaction mechanisms have been proposed [Jiang10, Chen11a, Li11].

A crystal structure of MenB with bound O-succinylbenzoyl-aminoCoA (OSB-NCoA), a stable substrate analog, has been solved at 2 Å resolution. The structure reveals the position of all active site residues and supports a mechanism involving the direct participation of the two conserved Tyr residues Y97 and Y258 in the intramolecular transfer of the substrate proton to the benzylic carboxylate of the substrate [Li11].

Locations: cytosol

Map Position: [2,373,984 <- 2,374,841]

Molecular Weight of Polypeptide: 31.633 kD (from nucleotide sequence)

pI: 6.37

Unification Links: ASAP:ABE-0007476 , CGSC:519 , DIP:DIP-47854N , EchoBASE:EB1342 , EcoGene:EG11368 , EcoliWiki:b2262 , Mint:MINT-1227416 , ModBase:P0ABU0 , OU-Microarray:b2262 , PortEco:menB , PR:PRO_000023201 , Pride:P0ABU0 , Protein Model Portal:P0ABU0 , RefSeq:NP_416765 , RegulonDB:EG11368 , SMR:P0ABU0 , String:511145.b2262 , Swiss-Model:P0ABU0 , UniProt:P0ABU0

Relationship Links: InterPro:IN-FAMILY:IPR001753 , InterPro:IN-FAMILY:IPR010198 , InterPro:IN-FAMILY:IPR014748 , InterPro:IN-FAMILY:IPR018376 , InterPro:IN-FAMILY:IPR029045 , PDB:Structure:3T88 , PDB:Structure:3T89 , PDB:Structure:4ELS , PDB:Structure:4ELW , PDB:Structure:4ELX , PDB:Structure:4I42 , Pfam:IN-FAMILY:PF00378 , Prosite:IN-FAMILY:PS00166

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Biological Process: GO:0009234 - menaquinone biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, UniProtGOA11, GOA06, GOA01, Young75]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Butland05]
GO:0008935 - 1,4-dihydroxy-2-naphthoyl-CoA synthase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Sharma92, Jiang10, Heide82]
GO:0071890 - bicarbonate binding Inferred from experiment [Jiang10]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, LopezCampistrou05]

MultiFun Terms: metabolism biosynthesis of building blocks cofactors, small molecule carriers menaquinone, ubiquinone
metabolism energy metabolism, carbon anaerobic respiration

Credits:
Created in EcoCyc 27-Jul-2010 by Keseler I , SRI International
Imported from EcoCyc 02-Jun-2015 by Paley S , SRI International


Enzymatic reaction of: 1,4-dihydroxy-2-naphthoyl-CoA synthase

Synonyms: dihydroxynaphthoate synthase, DHNA synthase, o-succinylbenzoyl-CoA 1,4-dihydroxy-2-naphthoate-lyase (cyclizing), naphthoate-CoA synthase, DHNA-CoA synthase

EC Number: 4.1.3.36

4-(2'-carboxyphenyl)-4-oxobutyryl-CoA + H+ <=> 1,4-dihydroxy-2-naphthoyl-CoA + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is irreversible in the direction shown. [Chen11a]

In Pathways: superpathway of menaquinol-8 biosynthesis I , superpathway of demethylmenaquinol-8 biosynthesis , superpathway of chorismate metabolism , 1,4-dihydroxy-2-naphthoate biosynthesis I

Credits:
Imported from EcoCyc 02-Jun-2015 by Paley S , SRI International

Summary:
Nitrate is a competitive inhibitor with respect to the bicarbonate cofactor [Jiang10].

MenB and DHNA-CoA form a tight complex with a dissociation constant of less than 500 nM [Chen11a].

Cofactors or Prosthetic Groups: hydrogen carbonate [Jiang10]

Inhibitors (Competitive): 1,4-dihydroxy-2-naphthoyl-CoA (Kic = 1.5µM) [Chen11a] , nitrate [Jiang10]

Kinetic Parameters:

Substrate
Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)
Citations
4-(2'-carboxyphenyl)-4-oxobutyryl-CoA
25.9
0.062, 620.0
0.0024, 23.94
[Li11, BRENDA14]


Sequence Features

Feature Class Location Citations Comment
Amino-Acid-Sites-That-Bind 45
[Sun13, Li11, UniProt14]
UniProt: Substrate.
Protein-Segment 84 -> 89
[Sun13, Li11, UniProt14]
UniProt: Substrate binding; Sequence Annotation Type: region of interest.
Mutagenesis-Variant 89
[Sun13, UniProt14]
UniProt: Strongly decreases affinity for substrate and DHNA-CoA synthase activity.
Mutagenesis-Variant 91
[Sun13, UniProt14]
UniProt: Loss of DHNA-CoA synthase activity.
Mutagenesis-Variant 97
[Li11, UniProt14]
UniProt: Loss of DHNA-CoA synthase activity.
Amino-Acid-Sites-That-Bind 97
[Li11, UniProt14]
UniProt: Substrate.
Protein-Segment 129 -> 133
[UniProt11]
UniProt: Substrate binding; Sequence Annotation Type: region of interest; Non-Experimental Qualifier: by similarity.
Mutagenesis-Variant 154
[Jiang10, UniProt11]
UniProt: Reduces the specific DHNA-CoA synthase activity by 15-fold, whereas its affinity for bicarbonate is reduced by 36-fold.
Protein-Segment 154 -> 156
[UniProt11]
UniProt: Bicarbonate binding; Sequence Annotation Type: region of interest; Non-Experimental Qualifier: by similarity.
Amino-Acid-Sites-That-Bind 155
[Sun13, Li11, UniProt15]
UniProt: Substrate.
Mutagenesis-Variant 156
[Jiang10, UniProt11]
UniProt: Loss of DHNA-CoA synthase activity.
Amino-Acid-Sites-That-Bind 161
[Sun13, UniProt15]
UniProt: Substrate.
Mutagenesis-Variant 163
[Chen11a]
D > A mutation causes loss of activity and loss of ligand binding ability [Chen11a].
Mutagenesis-Variant 184
[Jiang10, UniProt11]
UniProt: Reduces the specific DHNA-CoA synthase activity by 530-fold, whereas its affinity for bicarbonate is reduced by 20-fold.
Amino-Acid-Sites-That-Bind 258
[Li11, UniProt14]
UniProt: Substrate; shared with neighboring subunit.
Mutagenesis-Variant 267
[Sun13, UniProt14]
UniProt: Strongly decreases affinity for substrate and DHNA-CoA synthase activity.
Mutagenesis-Variant 270
[Sun13, UniProt14]
UniProt: Strongly decreases affinity for substrate and DHNA-CoA synthase activity.
Mutagenesis-Variant 273
[Sun13, UniProt14]
UniProt: Impairs protein folding.
Amino-Acid-Sites-That-Bind 273
[Sun13, Li11, UniProt14]
UniProt: Substrate; shared with neighboring subunit.

History:
10/20/97 Gene b2262 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11368; confirmed by SwissProt match.


References

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Chen11a: Chen M, Jiang M, Sun Y, Guo ZF, Guo Z (2011). "Stabilization of the second oxyanion intermediate by 1,4-dihydroxy-2-naphthoyl-coenzyme A synthase of the menaquinone pathway: spectroscopic evidence of the involvement of a conserved aspartic acid." Biochemistry 50(26);5893-904. PMID: 21627110

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Heide82: Heide L, Arendt S, Leistner E (1982). "Enzymatic synthesis, characterization, and metabolism of the coenzyme A ester of o-succinylbenzoic acid, an intermediate in menaquinone (vitamin K2) biosynthesis." J Biol Chem 1982;257(13);7396-400. PMID: 7045104

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Jiang10: Jiang M, Chen M, Guo ZF, Guo Z (2010). "A bicarbonate cofactor modulates 1,4-dihydroxy-2-naphthoyl-coenzyme a synthase in menaquinone biosynthesis of Escherichia coli." J Biol Chem 285(39);30159-69. PMID: 20643650

Li11: Li HJ, Li X, Liu N, Zhang H, Truglio JJ, Mishra S, Kisker C, Garcia-Diaz M, Tonge PJ (2011). "Mechanism of the intramolecular Claisen condensation reaction catalyzed by MenB, a crotonase superfamily member." Biochemistry 50(44);9532-44. PMID: 21830810

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Meganathan81: Meganathan R, Bentley R (1981). "Biosynthesis of o-succinylbenzoic acid in a men- Escherichia coli mutant requires decarboxylation of L-glutamate at the C-1 position." Biochemistry 20(18);5336-40. PMID: 6117313

Sharma92: Sharma V, Suvarna K, Meganathan R, Hudspeth ME (1992). "Menaquinone (vitamin K2) biosynthesis: nucleotide sequence and expression of the menB gene from Escherichia coli." J Bacteriol 1992;174(15);5057-62. PMID: 1629162

Shaw82: Shaw DJ, Guest JR, Meganathan R, Bentley R (1982). "Characterization of Escherichia coli men mutants defective in conversion of o-succinylbenzoate to 1,4-dihydroxy-2-naphthoate." J Bacteriol 152(3);1132-7. PMID: 6754698

Sun13: Sun Y, Song H, Li J, Li Y, Jiang M, Zhou J, Guo Z (2013). "Structural basis of the induced-fit mechanism of 1,4-dihydroxy-2-naphthoyl coenzyme A synthase from the crotonase fold superfamily." PLoS One 8(4);e63095. PMID: 23658663

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProt14: UniProt Consortium (2014). "UniProt version 2014-08 released on 2014-08-01 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

Young75: Young IG (1975). "Biosynthesis of bacterial menaquinones. Menaquinone mutants of Escherichia coli." Biochemistry 14(2);399-406. PMID: 1091286


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.0 on Mon Aug 31, 2015, biocyc14.