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Escherichia coli K-12 substr. MG1655 Enzyme: hydroxymethylpyrimidine kinase / phosphohydroxymethylpyrimidine kinase



Gene: thiD Accession Numbers: G7135 (EcoCyc), b2103, ECK2096

Synonyms: thiN, thiA, thiJ, hydroxymethylpyrimidine kinase 2

Regulation Summary Diagram: ?

Subunit composition of hydroxymethylpyrimidine kinase / phosphohydroxymethylpyrimidine kinase = [ThiD]4

Summary:
Hydroxymethylpyrimidine (HMP) kinase is involved in the biosynthesis of thiamine phosphate. This enzyme catalyzes the conversion of hydroxymethylpyrimidine to its monophosphate (HMP-P) in the presence of ATP. Subsequently, this enzyme catalyzes the conversion of HMP-P to hydroxymethylpyrimidine pyrophosphate (HMP-PP). Therefore, HMP kinase is a bifunctional enzyme catalyzing both HMP kinase and HMP-P kinase reactions. [Mizote89, Mizote99, Reddick98]

There are two HMP kinases in E. coli, the HMP kinase described above is encoded by the thiD gene and the other HMP kinase, also referred to as pyridoxal or pyridoxamine kinase (PdxK), is encoded by the pdxK gene product. Mutations in both genes in the same cell resulted in the complete loss of HMP kinase activity [Mizote96].

Under anaerobiosis, FNR represses thiD gene expression, but it is not known if this regulation is direct or indirect [Salmon03].

Locations: cytosol

Map Position: [2,181,738 <- 2,182,538] (47.02 centisomes)
Length: 801 bp / 266 aa

Molecular Weight of Polypeptide: 28.634 kD (from nucleotide sequence), 43.0 kD (experimental) [Mizote89 ]

Unification Links: ASAP:ABE-0006958 , DIP:DIP-6867N , EchoBASE:EB3821 , EcoGene:EG14068 , EcoGene:EG20225 , EcoliWiki:b2103 , ModBase:P76422 , OU-Microarray:b2103 , PortEco:thiD , PR:PRO_000024053 , Pride:P76422 , Protein Model Portal:P76422 , RefSeq:NP_416606 , RegulonDB:G7135 , SMR:P76422 , String:511145.b2103 , Swiss-Model:P76422 , UniProt:P76422

Relationship Links: InterPro:IN-FAMILY:IPR004399 , InterPro:IN-FAMILY:IPR013749 , Pfam:IN-FAMILY:PF08543

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0009228 - thiamine biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01, Mizote99]
GO:0009229 - thiamine diphosphate biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, Mizote99]
GO:0016310 - phosphorylation Inferred from experiment Inferred by computational analysis [UniProtGOA11, Mizote89]
Molecular Function: GO:0008902 - hydroxymethylpyrimidine kinase activity Inferred from experiment Inferred by computational analysis [GOA01a, Mizote89]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11]
GO:0008972 - phosphomethylpyrimidine kinase activity Inferred by computational analysis [GOA01a, GOA01]
GO:0016301 - kinase activity Inferred by computational analysis [UniProtGOA11]
GO:0016740 - transferase 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 thiamin

Essentiality data for thiD 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]
Yes [Feist07, Comment 4]

Credits:
Last-Curated ? 01-Aug-2013 by Kubo A , SRI International


Enzymatic reaction of: hydroxymethylpyrimidine kinase

Synonyms: ATP:4-amino-5-hydroxymethyl-2-methylpyrimidine 5-phosphotransferase, HMP kinase

EC Number: 2.7.1.49

ATP + hydroxymethylpyrimidine <=> ADP + 4-amino-2-methyl-5-phosphomethylpyrimidine + 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.

In Pathways: thiamin salvage II , hydroxymethylpyrimidine salvage

Inhibitors (Competitive): pyridoxine (Kic = 2.7µM) [Mizote89]

Kinetic Parameters:

Substrate
Km (μM)
Citations
hydroxymethylpyrimidine
66.0
[Mizote89]

pH(opt): 6.0 [Mizote89]


Enzymatic reaction of: phosphohydroxymethylpyrimidine kinase

Synonyms: ATP:4-amino-2methyl-5-phosphomethylpyrimidine phosphotransferase, 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase, HMP-P kinase

EC Number: 2.7.4.7

4-amino-2-methyl-5-phosphomethylpyrimidine + ATP <=> 4-amino-2-methyl-5-diphosphomethylpyrimidine + ADP

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.

In Pathways: superpathway of thiamin diphosphate biosynthesis I , thiamin salvage II , 4-amino-2-methyl-5-diphosphomethylpyrimidine biosynthesis , hydroxymethylpyrimidine salvage


Sequence Features

Feature Class Location Citations Comment
Amino-Acid-Sites-That-Bind 44
[UniProt10a]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
3/2/1998 (pkarp) Merged genes G193/EG20225 and G7135/thiD
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


References

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

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

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

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.

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

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

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

Mizote89: Mizote T, Nakayama H (1989). "Purification and properties of hydroxymethylpyrimidine kinase from Escherichia coli." Biochim Biophys Acta 1989;991(1);109-13. PMID: 2540841

Mizote96: Mizote T, Tsuda M, Nakazawa T, Nakayama H (1996). "The thiJ locus and its relation to phosphorylation of hydroxymethylpyrimidine in Escherichia coli." Microbiology 1996;142 ( Pt 10);2969-74. PMID: 8885414

Mizote99: Mizote T, Tsuda M, Smith DD, Nakayama H, Nakazawa T (1999). "Cloning and characterization of the thiD/J gene of Escherichia coli encoding a thiamin-synthesizing bifunctional enzyme, hydroxymethylpyrimidine kinase/phosphomethylpyrimidine kinase." Microbiology 1999;145 ( Pt 2);495-501. PMID: 10075431

Reddick98: Reddick JJ, Kinsland C, Nicewonger R, Christian T, Downs DM, Winkler ME, Begley TP "Overexpression, purification and characterization of two pyrimidine kinases involved in the biosynthesis of thiamin: 4-amino-5-hydroxymethyl-2-methylpyrimidine kinase and 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase." Tetrahedron 54:15983-15991 (1998).

Salmon03: Salmon K, Hung SP, Mekjian K, Baldi P, Hatfield GW, Gunsalus RP (2003). "Global gene expression profiling in Escherichia coli K12. The effects of oxygen availability and FNR." J Biol Chem 278(32);29837-55. PMID: 12754220

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 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."

Other References Related to Gene Regulation

Edwards06: Edwards TE, Ferre-D'Amare AR (2006). "Crystal structures of the thi-box riboswitch bound to thiamine pyrophosphate analogs reveal adaptive RNA-small molecule recognition." Structure 14(9);1459-68. PMID: 16962976

Kulshina10: Kulshina N, Edwards TE, Ferre-D'Amare AR (2010). "Thermodynamic analysis of ligand binding and ligand binding-induced tertiary structure formation by the thiamine pyrophosphate riboswitch." RNA 16(1);186-96. PMID: 19948769

Lang07: Lang K, Rieder R, Micura R (2007). "Ligand-induced folding of the thiM TPP riboswitch investigated by a structure-based fluorescence spectroscopic approach." Nucleic Acids Res 35(16);5370-8. PMID: 17693433

MendozaVargas09: Mendoza-Vargas A, Olvera L, Olvera M, Grande R, Vega-Alvarado L, Taboada B, Jimenez-Jacinto V, Salgado H, Juarez K, Contreras-Moreira B, Huerta AM, Collado-Vides J, Morett E (2009). "Genome-wide identification of transcription start sites, promoters and transcription factor binding sites in E. coli." PLoS One 4(10);e7526. PMID: 19838305

MirandaRios07: Miranda-Rios J (2007). "The THI-box riboswitch, or how RNA binds thiamin pyrophosphate." Structure 15(3);259-65. PMID: 17355861

Noeske06: Noeske J, Richter C, Stirnal E, Schwalbe H, Wohnert J (2006). "Phosphate-group recognition by the aptamer domain of the thiamine pyrophosphate sensing riboswitch." Chembiochem 7(9);1451-6. PMID: 16871614

OntiverosPalaci08: Ontiveros-Palacios N, Smith AM, Grundy FJ, Soberon M, Henkin TM, Miranda-Rios J (2008). "Molecular basis of gene regulation by the THI-box riboswitch." Mol Microbiol 67(4);793-803. PMID: 18179415

Rentmeister07: Rentmeister A, Mayer G, Kuhn N, Famulok M (2007). "Conformational changes in the expression domain of the Escherichia coli thiM riboswitch." Nucleic Acids Res 35(11);3713-22. PMID: 17517779

Serganov06: Serganov A, Polonskaia A, Phan AT, Breaker RR, Patel DJ (2006). "Structural basis for gene regulation by a thiamine pyrophosphate-sensing riboswitch." Nature 441(7097);1167-71. PMID: 16728979

Winkler02: Winkler W, Nahvi A, Breaker RR (2002). "Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression." Nature 419(6910);952-6. PMID: 12410317


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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 18.5 on Sun Dec 21, 2014, biocyc14.