XPB
XPB (xeroderma pigmentosum tip B) je ATP-ovisna DNK helikaza , kod ljudi koji je dio kompleksa transkripcijskog faktora TFIIH, Kod ljudi, gen XPB nalazi se na hromosomu 2.
Struktura[uredi | uredi izvor]
Dr. John Tainer i njegova grupa u The Scripps Research Institute riješili su 3D strukturu arhejskog homologa XPB rendgenskom kristalografijom.[5]
Aminokiselinska sekvenca[uredi | uredi izvor]
Dužina polipeptidnog lanca je 782 aminokiseline, a molekulska težina 89.278 Da.[5]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MGKRDRADRD | KKKSRKRHYE | DEEDDEEDAP | GNDPQEAVPS | AAGKQVDESG | ||||
| TKVDEYGAKD | YRLQMPLKDD | HTSRPLWVAP | DGHIFLEAFS | PVYKYAQDFL | ||||
| VAIAEPVCRP | THVHEYKLTA | YSLYAAVSVG | LQTSDITEYL | RKLSKTGVPD | ||||
| GIMQFIKLCT | VSYGKVKLVL | KHNRYFVESC | HPDVIQHLLQ | DPVIRECRLR | ||||
| NSEGEATELI | TETFTSKSAI | SKTAESSGGP | STSRVTDPQG | KSDIPMDLFD | ||||
| FYEQMDKDEE | EEEETQTVSF | EVKQEMIEEL | QKRCIHLEYP | LLAEYDFRND | ||||
| SVNPDINIDL | KPTAVLRPYQ | EKSLRKMFGN | GRARSGVIVL | PCGAGKSLVG | ||||
| VTAACTVRKR | CLVLGNSAVS | VEQWKAQFKM | WSTIDDSQIC | RFTSDAKDKP | ||||
| IGCSVAISTY | SMLGHTTKRS | WEAERVMEWL | KTQEWGLMIL | DEVHTIPAKM | ||||
| FRRVLTIVQA | HCKLGLTATL | VREDDKIVDL | NFLIGPKLYE | ANWMELQNNG | ||||
| YIAKVQCAEV | WCPMSPEFYR | EYVAIKTKKR | ILLYTMNPNK | FRACQFLIKF | ||||
| HERRNDKIIV | FADNVFALKE | YAIRLNKPYI | YGPTSQGERM | QILQNFKHNP | ||||
| KINTIFISKV | GDTSFDLPEA | NVLIQISSHG | GSRRQEAQRL | GRVLRAKKGM | ||||
| VAEEYNAFFY | SLVSQDTQEM | AYSTKRQRFL | VDQGYSFKVI | TKLAGMEEED | ||||
| LAFSTKEEQQ | QLLQKVLAAT | DLDAEEEVVA | GEFGSRSSQA | SRRFGTMSSM | ||||
| SGADDTVYME | YHSSRSKAPS | KHVHPLFKRF | RK |
Funkcija[uredi | uredi izvor]
XPB ima značajnu ulogu u normalnoj baznoj transkripciji, transkripcijski spojenom popravku (TCR) i popravak ekscizijom nukleotida (NER). Pokazalo se da pročišćeni XPB odmotava DNK sa 3’-5’ polarnosti.
Funkcija XPB(ERCC3) proteina u NER-u je da pomogne u odmotavanju DNK dvostruke spirale nakon što se oštećenje prvobitno prepozna. NER je put u više koraka koji uklanja širok spektar različitih oštećenja DNK koja narušavaju normalno uparivanje baza. Takva oštećenja uključuju glomazne hemijske adukte, UV-inducirane pirimidinske dimere i nekoliko oblika oksidativnog oštećenja. Mutacije gena XPB(ERCC3) mogu kod ljudi dovesti do bolesti xeroderma pigmentosum (XP) ili XP u kombinaciji sa Cockayneovim sindromom (XPCS).[6] Mutantne XPB ćelije pojedinaca sa XPCS fenotipom su osjetljive na UV-zračenje i akutni oksidativni stres.[7]
Poremećaji[uredi | uredi izvor]
Mutacije u XPB i drugim srodnim komplementarnim grupama, XPA-XPG, dovode do brojnih genetički poremećaj|genetičkih poremećaja]] kao što su Xeroderma pigmentosum, Cockayneov sindrom i trihotiodistrofija.
Interakcije[uredi | uredi izvor]
Pokazalo se da je XPB u interakciji sa:
Inhibitori malih molekula[uredi | uredi izvor]
Snažni, bioaktivni prirodni proizvodi poput triptolida koji inhibiraju transkripciju sisara putem inhibicije XPB podjedinice općeg transkripcijskog faktora TFIIH nedavno su prijavljeni kao konjugat glukoze za ciljanje hipoksijskih ćelija raka s povećanom ekspresijom transportera glukoze.[18]
Također pogledajte[uredi | uredi izvor]
- Xeroderma pigmentosum, komplementarna grupa G
Reference[uredi | uredi izvor]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000163161 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024382 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b Fan L, Arvai AS, Cooper PK, Iwai S, Hanaoka F, Tainer JA (april 2006). "Conserved XPB Core Structure and Motifs for DNA Unwinding: Implications for Pathway Selection of Transcription or Excision Repair". Molecular Cell. 22 (1): 27–37. doi:10.1016/j.molcel.2006.02.017. PMID 16600867.
- ^ Oh KS, Khan SG, Jaspers NG, Raams A, Ueda T, Lehmann A, Friedmann PS, Emmert S, Gratchev A, Lachlan K, Lucassan A, Baker CC, Kraemer KH (2006). "Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome". Hum. Mutat. 27 (11): 1092–103. doi:10.1002/humu.20392. PMID 16947863. S2CID 22852219.
- ^ Andressoo JO, Weeda G, de Wit J, Mitchell JR, Beems RB, van Steeg H, van der Horst GT, Hoeijmakers JH (2009). "An Xpb mouse model for combined xeroderma pigmentosum and cockayne syndrome reveals progeroid features upon further attenuation of DNA repair". Mol. Cell. Biol. 29 (5): 1276–90. doi:10.1128/MCB.01229-08. PMC 2643825. PMID 19114557.
- ^ Takeda N, Shibuya M, Maru Y (januar 1999). "The BCR-ABL oncoprotein potentially interacts with the xeroderma pigmentosum group B protein". Proc. Natl. Acad. Sci. U.S.A. 96 (1): 203–7. Bibcode:1999PNAS...96..203T. doi:10.1073/pnas.96.1.203. PMC 15117. PMID 9874796.
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- ^ a b Rossignol M, Kolb-Cheynel I, Egly JM (april 1997). "Substrate specificity of the cdk-activating kinase (CAK) is altered upon association with TFIIH". EMBO J. 16 (7): 1628–37. doi:10.1093/emboj/16.7.1628. PMC 1169767. PMID 9130708.
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- ^ a b c d Marinoni JC, Roy R, Vermeulen W, Miniou P, Lutz Y, Weeda G, Seroz T, Gomez DM, Hoeijmakers JH, Egly JM (mart 1997). "Cloning and characterization of p52, the fifth subunit of the core of the transcription/DNA repair factor TFIIH". EMBO J. 16 (5): 1093–102. doi:10.1093/emboj/16.5.1093. PMC 1169708. PMID 9118947.
- ^ Drapkin R, Reardon JT, Ansari A, Huang JC, Zawel L, Ahn K, Sancar A, Reinberg D (april 1994). "Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II". Nature. 368 (6473): 769–72. Bibcode:1994Natur.368..769D. doi:10.1038/368769a0. PMID 8152490. S2CID 4363484.
- ^ Iyer N, Reagan MS, Wu KJ, Canagarajah B, Friedberg EC (februar 1996). "Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein". Biochemistry. 35 (7): 2157–67. doi:10.1021/bi9524124. PMID 8652557.
- ^ Wang XW, Yeh H, Schaeffer L, Roy R, Moncollin V, Egly JM, Wang Z, Freidberg EC, Evans MK, Taffe BG (juni 1995). "p53 modulation of TFIIH-associated nucleotide excision repair activity". Nat. Genet. 10 (2): 188–95. doi:10.1038/ng0695-188. hdl:1765/54884. PMID 7663514. S2CID 38325851.
- ^ Weeda G, Rossignol M, Fraser RA, Winkler GS, Vermeulen W, van 't Veer LJ, Ma L, Hoeijmakers JH, Egly JM (juni 1997). "The XPB subunit of repair/transcription factor TFIIH directly interacts with SUG1, a subunit of the 26S proteasome and putative transcription factor". Nucleic Acids Res. 25 (12): 2274–83. doi:10.1093/nar/25.12.2274. PMC 146752. PMID 9173976.
- ^ Yokoi M, Masutani C, Maekawa T, Sugasawa K, Ohkuma Y, Hanaoka F (mart 2000). "The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA". J. Biol. Chem. 275 (13): 9870–5. doi:10.1074/jbc.275.13.9870. PMID 10734143.
- ^ Datan E, Minn I, Peng X, He QL, Ahn H, Yu B, Pomper MG, Liu JO (2020). "A Glucose-Triptolide Conjugate Selectively Targets Cancer Cells under Hypoxia". iScience. 23 (9): 101536. Bibcode:2020iSci...23j1536D. doi:10.1016/j.isci.2020.101536. PMC 7509213. PMID 33083765.
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Vanjski linkovi[uredi | uredi izvor]
- GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum
- XPBC-ERCC-3 protein na US National Library of Medicine Medical Subject Headings (MeSH)
