ジヒドロプテロイン酸合成酵素、ジヒドロプテロイン酸シンターゼ
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2016/03/16 14:16:26」(JST)
[Wiki en表示]
Dihydropteroate synthase |
Tetrahydrofolate synthesis pathway
|
Identifiers |
EC number |
2.5.1.15 |
CAS number |
9055-61-2 |
Databases |
IntEnz |
IntEnz view |
BRENDA |
BRENDA entry |
ExPASy |
NiceZyme view |
KEGG |
KEGG entry |
MetaCyc |
metabolic pathway |
PRIAM |
profile |
PDB structures |
RCSB PDB PDBe PDBsum |
Gene Ontology |
AmiGO / EGO |
Search |
PMC |
articles |
PubMed |
articles |
NCBI |
proteins |
|
Pterin binding enzyme |
Identifiers |
Symbol |
Pterin_bind |
Pfam |
PF00809 |
InterPro |
IPR000489 |
PROSITE |
PDOC00630 |
SCOP |
1ajz |
SUPERFAMILY |
1ajz |
Available protein structures: |
Pfam |
structures |
PDB |
RCSB PDB; PDBe; PDBj |
PDBsum |
structure summary |
|
Dihydropteroate synthase is an enzyme classified under EC 2.5.1.15. It produces dihydropteroate in bacteria, but it is not expressed in most eukaryotes including humans. This makes it a useful target for sulfonamide antibiotics, which compete with the PABA precursor.
- (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate + 4-aminobenzoate (PABA) diphosphate + dihydropteroate.
All organisms require reduced folate cofactors for the synthesis of a variety of metabolites. Most microorganisms must synthesize folate de novo because they lack the active transport system of higher vertebrate cells that allows these organisms to use dietary folates. Proteins containing this domain include dihydropteroate synthase (EC 2.5.1.15) as well as a group of methyltransferase enzymes including methyltetrahydrofolate, corrinoid iron-sulphur protein methyltransferase (MeTr) Q46389 that catalyses a key step in the Wood-Ljungdahl pathway of carbon dioxide fixation.
Dihydropteroate synthase (EC 2.5.1.15) (DHPS) catalyses the condensation of 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate to para-aminobenzoic acid to form 7,8-dihydropteroate. This is the second step in the three-step pathway leading from 6-hydroxymethyl-7,8-dihydropterin to 7,8-dihydrofolate. DHPS is the target of sulphonamides, which are substrate analogues that compete with para-aminobenzoic acid. Bacterial DHPS (gene sul or folP)[1] is a protein of about 275 to 315 amino acid residues that is either chromosomally encoded or found on various antibiotic resistance plasmids. In the lower eukaryote Pneumocystis carinii, DHPS is the C-terminal domain of a multifunctional folate synthesis enzyme (gene fas).[2]
References
- ^ Crawford IP, Slock J, Stahly DP, Six EW, Han CY (1990). "An apparent Bacillus subtilis folic acid biosynthetic operon containing pab, an amphibolic trpG gene, a third gene required for synthesis of para-aminobenzoic acid, and the dihydropteroate synthase gene". J. Bacteriol. 172 (12): 7211–7226. PMC 210846. PMID 2123867.
- ^ Volpe F, Dyer M, Scaife JG, Darby G, Stammers DK, Delves CJ (1992). "The multifunctional folic acid synthesis fas gene of Pneumocystis carinii appears to encode dihydropteroate synthase and hydroxymethyldihydropterin pyrophosphokinase". Gene 112 (2): 213–218. doi:10.1016/0378-1119(92)90378-3. PMID 1313386.
External links
- Dihydropteroate synthetase at the US National Library of Medicine Medical Subject Headings (MeSH)
Metabolism of vitamins, coenzymes, and cofactors
|
|
Fat soluble vitamins |
Vitamin A |
|
|
Vitamin E |
- Alpha-tocopherol transfer protein
|
|
Vitamin D |
- liver (Sterol 27-hydroxylase or CYP27A1)
- renal (25-Hydroxyvitamin D3 1-alpha-hydroxylase or CYP27B1)
- degradation (1,25-Dihydroxyvitamin D3 24-hydroxylase or CYP24A1)
|
|
Vitamin K |
- Vitamin K epoxide reductase
|
|
|
Water soluble vitamins |
Thiamine (B1) |
|
|
Niacin (B3) |
- Indoleamine 2,3-dioxygenase
- Formamidase
|
|
Pantothenic acid (B5) |
|
|
Folic acid (B9) |
- Dihydropteroate synthase
- Dihydrofolate reductase
- Serine hydroxymethyltransferase
|
|
- Methylenetetrahydrofolate reductase
|
|
|
Vitamin B12 |
|
|
Vitamin C |
|
|
Riboflavin (B2) |
|
|
|
Nonvitamin cofactors |
Tetrahydrobiopterin |
- GTP cyclohydrolase I
- 6-pyruvoyltetrahydropterin synthase
- Sepiapterin reductase
|
|
|
|
|
Molybdenum cofactor |
- MOCS1
- MOCS2
- MOCS3
- Gephyrin
|
|
|
Transferases: alkyl and aryl (EC 2.5)
|
|
2.5.1 |
- Dimethylallyltranstransferase
- Thiaminase I
- Methionine adenosyltransferase
- Riboflavin synthase
- Dihydropteroate synthase
- Spermidine synthase
- Glutathione S-transferase
- Farnesyl-diphosphate farnesyltransferase
- Spermine synthase
- Alkylglycerone phosphate synthase
- Farnesyltransferase
- Geranylgeranyltransferase type 1
- Porphobilinogen deaminase
|
|
Proteins: enzymes
|
|
Activity |
- Active site
- Binding site
- Catalytic triad
- Oxyanion hole
- Enzyme promiscuity
- Catalytically perfect enzyme
- Coenzyme
- Cofactor
- Enzyme catalysis
- Enzyme kinetics
- Lineweaver–Burk plot
- Michaelis–Menten kinetics
|
|
Regulation |
- Allosteric regulation
- Cooperativity
- Enzyme inhibitor
|
|
Classification |
- EC number
- Enzyme superfamily
- Enzyme family
- List of enzymes
|
|
Types |
- EC1 Oxidoreductases(list)
- EC2 Transferases(list)
- EC3 Hydrolases(list)
- EC4 Lyases(list)
- EC5 Isomerases(list)
- EC6 Ligases(list)
|
|
This article incorporates text from the public domain Pfam and InterPro IPR000489
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- Pneumocystis jirovecii dihydropteroate synthase gene mutations in a group of HIV-negative immunocompromised patients with Pneumocystis pneumonia.
- Long Y, Zhang C, Su L, Que C.
- Experimental and therapeutic medicine.Exp Ther Med.2014 Dec;8(6):1825-1830. Epub 2014 Oct 3.
- The purpose of this study was to investigate dihydropteroate synthase (DHPS) mutations and their clinical context in non-HIV-infected patients with Pneumocystis pneumonia (PCP). DHPS genes in respiratory samples collected from HIV-negative patients with PCP presented between January 2008 and April 2
- PMID 25371739
- Structure-Based Design and Development of Functionalized Mercaptoguanine Derivatives as Inhibitors of the Folate Biosynthesis Pathway Enzyme 6-Hydroxymethyl-7,8-dihydropterin Pyrophosphokinase from Staphylococcus aureus.
- Dennis ML1, Chhabra S, Wang ZC, Debono A, Dolezal O, Newman J, Pitcher NP, Rahmani R, Cleary B, Barlow N, Hattarki M, Graham B, Peat TS, Baell JB, Swarbrick JD.
- Journal of medicinal chemistry.J Med Chem.2014 Nov 26;57(22):9612-26. doi: 10.1021/jm501417f. Epub 2014 Nov 12.
- 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), an enzyme from the folate biosynthesis pathway, catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin and is a yet-to-be-drugged antimicrobial target. Building on our previous discovery that 8-mercaptoguanine (
- PMID 25357262
- AIDS-related Pneumocystis jirovecii genotypes in French Guiana.
- Le Gal S1, Blanchet D2, Damiani C3, Guéguen P4, Virmaux M5, Abboud P2, Guillot G2, Kérangart S5, Merle C5, Calderon E6, Totet A3, Carme B7, Nevez G8.
- Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.Infect Genet Evol.2014 Nov 5;29C:60-67. doi: 10.1016/j.meegid.2014.10.021. [Epub ahead of print]
- The study described Pneumocystis jirovecii (P. jirovecii) multilocus typing in seven AIDS patients living in French Guiana (Cayenne Hospital) and seven immunosuppressed patients living in Brest, metropolitan France (Brest Hospital). Archival P. jirovecii specimens were examined at the dihydropteroat
- PMID 25445659
Japanese Journal
- ニューモシスチスにおける薬物標的分子の変異と今後の展開
- 高橋 孝
- 日本医真菌学会雑誌 = Japanese journal of medical mycology 50(2), 67-73, 2009-04-30
- … ソキサゾールとトリメトプリム)合剤を第1選択として,ペンタミジンやアトバコンなどが第2選択として選択される.<I>Pc</I>に対する薬物標的は,(1)サルファメソキサゾール → dihydropteroate synthase(DHPS),(2)トリメトプリム → dihydrofolate reductase,(3)アトバコン → cytochrome <I>b</I>であり,その耐性機序として標的をコードする遺伝子変異がいわれている.特に,DHPSの活性中心で …
- NAID 10024793243
- 沖縄県の豚由来Toxoplasma gondiiの遺伝子型別(短報)(寄生虫病学)
- 座喜味 聡,喜屋 武向子,大城 守,杉本 千尋,藤崎 幸蔵
- The journal of veterinary medical science 68(4), 401-404, 2006-04-25
- … から得た有病変豚リンパ節101検体のDNAを抽出後,Toxoplasma gondiiのSAG2遺伝子をターゲットにnested PCRを実施したところ57検体が陽性だった.そのうち49が制限酵素による型別が可能で,22(44.9%)がI型,23(46.9%)がII型,4(8.2%)がIII型だった.またサルファ剤耐性と関連するとされるdihydropteroate synthase遺伝子がnested PCRにより57検体中40で増幅され,制限酵素パターンとシーケンスによるとこれらは全て野生型(感受性)だった. …
- NAID 110004758098
- 甲斐 雅規
- 日本ハンセン病学会雑誌 = Japanese journal of leprosy 73(3), 221-226, 2004-09-30
- … The relation between diaminodiphenylsulfone (called dapsone)-resistance and point mutations of the dihydropteroate synthase (DHPS) gene was analyzed using dapsone resistant <I>Mycobacterium leprae</I> …
- NAID 130000760206
Related Links
- I. Introduction Dihydropteroate synthase (DHPS) is an enzyme involved in the Bacillus anthracis folate synthesis pathway. The enzyme has two binding pockets: one which binds dihydropterin pyrophosphate (DHPP) and one which ...
- In bacteria, antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthase, DHPS. DHPS catalyses the conversion of PABA (para-aminobenzoate) to dihydropteroate, a key step in folate synthesis.
★リンクテーブル★
[★]
- 英
- dihydropteroate synthase
- 関
- ジヒドロプテロイン酸シンターゼ
[★]
- 英
- dihydropteroate synthase
- 関
- ジヒドロプテロイン酸合成酵素
[★]
- 関
- lyase、synthetase、transferase
[★]
ジヒドロプテロイン酸