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Escherichia coli K-12 substr. MG1655 Enzyme: 6-carboxy-5,6,7,8-tetrahydropterin synthase

Gene: queD Accession Numbers: G7431 (EcoCyc), b2765, ECK2760

Synonyms: ygcM, sscR

Regulation Summary Diagram: ?

Regulation summary diagram for queD

Subunit composition of 6-carboxy-5,6,7,8-tetrahydropterin synthase = [QueD]6
         6-carboxy-5,6,7,8-tetrahydropterin synthase = QueD

QueD converts 7,8-dihydroneopterin triphosphate (H2NTP) to 6-carboxy-5,6,7,8-tetrahydropterin (CPH4). Because queuosine is the only deazapurine produced in E. coli, CPH4 is likely an intermediate in the pathway of queuosine biosynthesis [McCarty09]. In initial in vitro studies under aerobic conditions, the enzyme was thought to catalyze 6-pyruvoyl tetrahydropterin synthesis [Woo02].

QueD belongs to the tunnel-fold superfamily of enzymes. Its mammalian homolog, 6-pyruvoyltetrahydropterin synthase (mPTPS), is required for the biosynthesis of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4), an essential cofactor for many enzymes. The structural basis for the differing substrate specificities of these closely related enzymes is therefore of interest, and crystal structures of the enzyme have been solved [Seo14, Miles14]. QueD consists of a hexamer of closely interacting trimers. Active site mutants have been analyzed for their activity [Seo14, Miles14]; two amino acid changes, W51M and F55L, can convert QueD to an enzyme with mammalian 6-pyruvoyltetrahydropterin synthase (PTPS) activity [Seo14]. A reaction mechanism has been proposed [Miles14].

Citations: [Seo08]

Locations: cytosol

Map Position: [2,890,236 -> 2,890,601] (62.29 centisomes, 224°)
Length: 366 bp / 121 aa

Molecular Weight of Polypeptide: 13.773 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0009068 , EchoBASE:EB2921 , EcoGene:EG13120 , EcoliWiki:b2765 , Mint:MINT-1299113 , ModBase:P65870 , OU-Microarray:b2765 , PortEco:queD , Protein Model Portal:P65870 , RefSeq:NP_417245 , RegulonDB:G7431 , SMR:P65870 , String:511145.b2765 , UniProt:P65870

Relationship Links: InterPro:IN-FAMILY:IPR007115 , Panther:IN-FAMILY:PTHR12589 , PDB:Structure:3QN0 , PDB:Structure:3QN9 , PDB:Structure:3QNA , PDB:Structure:4NTK , PDB:Structure:4NTM , PDB:Structure:4NTN , Pfam:IN-FAMILY:PF01242

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Biological Process: GO:0008616 - queuosine biosynthetic process Author statement Inferred by computational analysis [UniProtGOA11a, McCarty09]
Molecular Function: GO:0008270 - zinc ion binding Inferred from experiment [McCarty09]
GO:0042802 - identical protein binding Inferred from experiment [Seo14]
GO:0070497 - 6-carboxy-5,6,7,8-tetrahydropterin synthase activity Inferred from experiment [McCarty09]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: information transfer RNA related RNA modification

Essentiality data for queD knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Curated 13-Jan-2006 by Shearer A , SRI International
Revised 04-Jun-2014 by Keseler I , SRI International
Last-Curated ? 23-Dec-2014 by Keseler I , SRI International

Enzymatic reaction of: 6-carboxy-5,6,7,8-tetrahydropterin synthase

Synonyms: CTPS, CPH4 synthase

EC Number:

7,8-dihydroneopterin 3'-triphosphate + H2O <=> 6-carboxy-5,6,7,8-tetrahydropterin + PPPi + acetaldehyde + 2 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

Alternative Substrates for 7,8-dihydroneopterin 3'-triphosphate: 6-pyruvoyl tetrahydropterin [McCarty09 ] , sepiapterin [Seo14 , McCarty09 ]

In Pathways: preQ0 biosynthesis

Kinetic Parameters:

Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)

Sequence Features

Protein sequence of 6-carboxy-5,6,7,8-tetrahydropterin synthase with features indicated

Feature Class Location Citations Comment
Metal-Binding-Site 16
UniProt: Zinc; Non-Experimental Qualifier: by similarity;
Active-Site 27
UniProt: Proton acceptor; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 31
UniProt: Zinc; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 33
UniProt: Zinc; Non-Experimental Qualifier: by similarity;
Active-Site 71
UniProt: Charge relay system; Non-Experimental Qualifier: by similarity;
Active-Site 110
UniProt: Charge relay system; Non-Experimental Qualifier: by similarity;

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

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

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

McCarty09: McCarty RM, Somogyi A, Bandarian V (2009). "Escherichia coli QueD Is a 6-Carboxy-5,6,7,8-tetrahydropterin Synthase (dagger)." Biochemistry 48(11);2301-3. PMID: 19231875

Miles14: Miles ZD, Roberts SA, McCarty RM, Bandarian V (2014). "Biochemical and structural studies of 6-carboxy-5,6,7,8-tetrahydropterin synthase reveal the molecular basis of catalytic promiscuity within the tunnel-fold superfamily." J Biol Chem 289(34);23641-52. PMID: 24990950

Seo08: Seo KH, Supangat , Kim HL, Park YS, Jeon C, Lee KH (2008). "Purification, crystallization and preliminary crystallographic analysis of a 6-pyruvoyltetrahydropterin synthase homologue from Esherichia coli." Acta Crystallogr Sect F Struct Biol Cryst Commun 64(Pt 2);105-7. PMID: 18271114

Seo14: Seo KH, Zhuang N, Park YS, Park KH, Lee KH (2014). "Structural basis of a novel activity of bacterial 6-pyruvoyltetrahydropterin synthase homologues distinct from mammalian 6-pyruvoyltetrahydropterin synthase activity." Acta Crystallogr D Biol Crystallogr 70(Pt 5);1212-23. PMID: 24816091

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Woo02: Woo HJ, Hwang YK, Kim YJ, Kang JY, Choi YK, Kim CG, Park YS (2002). "Escherichia coli 6-pyruvoyltetrahydropterin synthase ortholog encoded by ygcM has a new catalytic activity for conversion of sepiapterin to 7,8-dihydropterin." FEBS Lett 523(1-3);234-8. PMID: 12123838

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 19.0 on Fri Sep 4, 2015, biocyc11.