Изворни код странице Dihidroorotat dehidrogenaza

{{Infobox Enzim-lat
| Name = Dihidroorotat oksidaza
| EC_number = 1.3.3.1
| CAS_number = 9029-03-2
| IUBMB_EC_number = 1/3/3/1
| GO_code = 000415
| image = 
| width = 
| caption = 
}}
{{Infobox Proteinska Familija-lat
| Symbol = DHO_dh
| Name = 
| image =1f76.gif
| width =
| caption =Dihidroorotat dehidrogenaza iz -{''[[E. coli]]''}-
| Pfam= PF01180
| InterPro= IPR001295
| SMART=
| PROSITE = PDOC00708
| SCOP = 1dor
| TCDB =
| OPM family= 59
| OPM protein= 1uum
| PDB=
{{PDB3|1f76}}A:47-336    {{PDB3|1uum}}A:77-377    {{PDB3|1uuo}}A:77-377
{{PDB3|1d3g}}A:77-377    {{PDB3|1d3h}}A:77-377    {{PDB3|2b0m}}A:77-377
{{PDB3|1lx3}}A:49-334    {{PDB3|1tv5}}A:207-550   {{PDB3|1ep3}}A:6-291
{{PDB3|1ep2}}A:6-291     {{PDB3|1ep1}}A:6-291     {{PDB3|1h7x}}A:532-838
{{PDB3|1gte}}A:532-838   {{PDB3|1h7w}}B:532-838   {{PDB3|1gth}}A:532-838
{{PDB3|1gt8}}A:532-838   {{PDB3|1jue}}A:1-293     {{PDB3|1jrb}}A:1-293
{{PDB3|1jub}}A:1-293     {{PDB3|1jqx}}A:1-293     {{PDB3|1jrc}}B:1-293
{{PDB3|2dor}}A:1-293     {{PDB3|1nfc}}A:1-293     {{PDB3|1jqv}}B:1-293
{{PDB3|1ovd}}B:1-293     {{PDB3|1dor}}A:1-293     {{PDB3|2b4g}}D:2-294
}}
{{Infobox protein-lat
|Name=Ljudska dihidroorotat dehidrogenaza
|caption=
|image=
|width=
|HGNCid=2867
|Symbol=DHODH
|AltSymbols=
|EntrezGene=1723
|OMIM=126064
|RefSeq=NM_001361
|UniProt=Q02127
|PDB=1D3G
|ECnumber=1.3.3.1
|Chromosome=16
|Arm=q
|Band=22
|LocusSupplementaryData=
}}

'''Dihidroorotat dehidrogenaza''' ({{EC broj-lat|1.3.3.1}}) je [[enzim]] koji katalizuje četvrti korak u ''de novo'' [[biosinteza pirimidina|biosintezi pirimidina]].<ref name="VoetBiochemistry3rd">{{VoetBiochemistry3rd |pages=1078-9}}</ref><ref>{{Cite book |author=Barry Steven Selinsky |title=Membrane Protein Protocols: Expression, Purification, and Characterization (Methods in Molecular Biology (Clifton, N.J.), V.228.) |url=https://archive.org/details/membraneproteinp00seli_303 |publisher=Humana Press |location=Totowa, NJ |year=2003 |isbn=978-1-58829-124-0 |chapter=2. Dihydroorotate Dehydrogenase of Escherichia coli |doi=10.1385/1-59259-400-X:11 |pages=[https://archive.org/details/membraneproteinp00seli_303/page/n10 11]-21 |accessdate=}}</ref> Ona pretvara [[dihidroorotat]] u [[orotat]]:

: -{(S)}--dihidroorotat + O<sub>2</sub> <math>\rightleftharpoons</math> orotate + -{H<sub>2</sub>O<sub>2</sub>}-

<gallery>
 Image:4,5-Dihydroorotic acid.svg|[[4,5-Dihidroorotična kiselina]]
 Image:Orotic acid.svg|[[Orotična kiselina]]. 
</gallery>

Ljudski dihidroorotat dehidrogenaza je sveprisutan [[Flavin mononukleotid|FMN]] [[flavoprotein]]. Kod bakterija (gen -{pyrD}-), se nalazi na unutarnjoj strani [[ćelijska membrana|ćelijske membrane]]. U nekim kvascima, kao kod ''-{[[Saccharomyces cerevisiae]]}-'' (gen URA1), to je citosolni [[protein]], dok se kod ostalih eukariota nalazi u mitohondrijima.<ref name="PUB00004801">{{cite journal |vauthors=Lacroute F, Thomas D, Nagy M |title=Divergent evolution of pyrimidine biosynthesis between anaerobic and aerobic yeasts |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue=19 |pages=8966–8970 |year=1992 |pmid=1409592 |doi=10.1073/pnas.89.19.8966}}</ref>.

== Kliničko značenje ==
Za antiupalni lek [[leflunomid]] je pokazano da inhibira -{DHODH}-. Ljudska -{DHODH}- ima dva [[Proteinski domen|domena]]: alfa/beta-barel domen koji sadrži aktivne stranice i alfa-spiralni domen koje formira otvaranje tunela koji vodi do aktivnog mesta<ref name="Rowland">{{cite journal | vauthors = Rowland P, Björnberg O, Nielsen FS, Jensen KF, Larsen S | title = The crystal structure of Lactococcus lactis dihydroorotate dehydrogenase A complexed with the enzyme reaction product throws light on its enzymatic function | journal = Protein Sci. | volume = 7 | issue = 6 | pages = 1269–79 | year = 1998 | pmid = 9655329 | pmc = 2144028 | doi = 10.1002/pro.5560070601 | url = http://www.proteinscience.org/cgi/content/abstract/7/6/1269 | access-date = 7. 05. 2010 | archive-url = https://web.archive.org/web/20081201092951/http://www.proteinscience.org/cgi/content/abstract/7/6/1269 | archive-date = 1. 12. 2008 |url-status=dead | df =  }}</ref>. Poznato je da se leflunomid vezuje u ovom tunelu.<ref name="pmid10673429">{{cite journal |vauthors=Liu S, Neidhardt EA, Grossman TH, Ocain T, Clardy J | title = Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents | journal = Structure | volume = 8 | issue = 1 | pages = 25–33 | year = 2000 | pmid = 10673429 | doi = 10.1016/S0969-2126(00)00077-0 | url =  }}</ref> Leflunomid se koristi za lečenje [[reumatoidni artritis|reumatoidnog artritisa]] i [[psorijaza|psorijaze]].<ref name="Foye">{{FoyePrinciplesMedChem5th |pages=785-6}}</ref><ref name="Goodman_Gilman">{{GoodmanGilman11th |chapter=Chapter 52. Immunosuppressants, tolerogens, and immunostimulants; Immunostimulation}}</ref>

Mutacije ovog gena su pokazane da uzrokuju [[Milerov sindrom]]<ref name="pmid19915526">{{cite journal |vauthors=Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ | title = Exome Sequencing identifies the cause of a mendelian disorder | journal = Nature Genetics | volume = 42 | issue = 1 | pages = 30–35 | year = 2009 | pmid = 19915526 |}}</ref> koji je isto tako poznat kao -{Genee-Wiedemann}- sindrom, -{Wildervanck-Smith}- sindrom ili [[post aksijalni akrofacijalni distosis]] (-{POADS}-).

== Vidi još ==
=== Ljudski proteini koji sadrže ove domene ===
* [[DHODH]]
* [[DPYD]]

== Reference ==
{{reflist}}

== Literatura ==
* {{Cite book |ref= harv|author=Barry Steven Selinsky |title=Membrane Protein Protocols: Expression, Purification, and Characterization (Methods in Molecular Biology (Clifton, N.J.), V.228.) |url= https://archive.org/details/membraneproteinp00seli_303|publisher=Humana Press |location=Totowa, NJ |year=2003 |isbn=978-1-58829-124-0 |chapter=2. Dihydroorotate Dehydrogenase of Escherichia coli |doi=10.1385/1-59259-400-X:11 |pages=[https://archive.org/details/membraneproteinp00seli_303/page/n10 11]-21 |accessdate=}}
== Spoljašnje veze ==
* {{MeSH name|dihydroorotate+dehydrogenase}}
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{{InterPro content-lat|IPR001295}}


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{{Podnožje|lat=da|Medicina|Hemija}}

[[Категорија:Proteinski domeni]]
[[Категорија:Periferni membranski proteini]]