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P-glikoprotein

Izvor: Wikipedija
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ATP-vezujuća kaseta, potfamilija B (MDR/TAP), član 1

Kristalografska struktura MDR3 proteina miša. Aproksimativna pozicija proteina u ćelijskoj membrani je obeležena plavim (ekstracelularno lice) i crvenim (citoplazmatično lice) linijama. Protein je prikaza u bojama duge (N-terminus = plavo, C-terminus = crveno). Ciklični peptidni inhibitor QZ59 je prikazan kao prostorno popunjavajući model.[1]
Dostupne strukture
3G5U, 3G60, 3G61
Identifikatori
SimboliABCB1; ABC20; CD243; CLCS; GP170; MDR1; P-GP; PGY1
Vanjski IDOMIM171050 MGI97570 HomoloGene55496 GeneCards: ABCB1 Gene
EC broj3.6.3.44
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez524318671
EnsemblENSG00000085563ENSMUSG00000040584
UniProtP08183P21447
RefSeq (mRNA)NM_000927.4NM_011076.2
RefSeq (protein)NP_000918.2NP_035206.2
Lokacija (UCSC)Chr 7:
87.13 - 87.34 Mb
Chr 5:
8.66 - 8.75 Mb
PubMed pretraga[1][2]

P-glikoprotein 1 (glikoprotein permeabilnosti, P-gp, Pgp, protein otpornosti na višestruke lekove 1, MDR1, ATP-vezujuća kaseta potfamilija B član 1, ABCB1, klaster of diferencijacije 243, CD243) je glikoprotein koji je kod ljudi kodiran ABCB1 genom.[2] P-gp dobro poznati ABC-transporter (koji transportuje široki opseg supstrata kroz ekstra- i intracelularne membrane). On je član MDR/TAP familije.[3]

Pgp je široko rasprostranjen i izražen u interstinalnom epitelu, hepatocitima, renalno proksimalno tubularnim ćelijama, nadbubrežnoj žlezdi i kapilarnim endotelnim ćelijama od kojih je formirana krvno-moždana i krvno-testikularna barijera.

Reference

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  1. PDB 3G60; Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G (March 2009). „Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding”. Science 323 (5922): 1718–22. DOI:10.1126/science.1168750. PMC 2720052. PMID 19325113. 
  2. Ueda K, Clark DP, Chen CJ, Roninson IB, Michael M. Gottesman, Pastan I (January 1987). „The human multidrug resistance (mdr1) gene. cDNA cloning and transcription initiation”. J. Biol. Chem. 262 (2): 505–8. PMID 3027054. Arhivirano iz originala na datum 2008-07-26. Pristupljeno 2014-05-27. 
  3. Dean, Michael (1. 11. 2002.). „The Human ATP-Binding Cassette (ABC) Transporter Superfamily”. National Library of Medicine (US), NCBI. Pristupljeno 2. 3. 2008. 

Literatura

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  • Kerb R, Hoffmeyer S, Brinkmann U (2001). „ABC drug transporters: hereditary polymorphisms and pharmacological impact in MDR1, MRP1 and MRP2”. Pharmacogenomics 2 (1): 51–64. DOI:10.1517/14622416.2.1.51. PMID 11258197. 
  • Akiyama S (2002). „[Mechanisms of drug resistance and reversal of the resistance]”. Hum. Cell 14 (4): 257–60. PMID 11925925. 
  • Brinkmann U (2002). „Functional polymorphisms of the human multidrug resistance (MDR1) gene: correlation with P glycoprotein expression and activity in vivo”. Novartis Found. Symp.. Novartis Foundation Symposia 243: 207–10; discussion 210–2, 231–5. DOI:10.1002/0470846356.ch15. ISBN 978-0-470-84635-3. PMID 11990778. 
  • Váradi A, Szakács G, Bakos E, Sarkadi B (2002). „P glycoprotein and the mechanism of multidrug resistance”. Novartis Found. Symp.. Novartis Foundation Symposia 243: 54–65; discussion 65–8, 180–5. DOI:10.1002/0470846356.ch5. ISBN 978-0-470-84635-3. PMID 11990782. 
  • Hegedus T, Orfi L, Seprodi A, et al. (2002). „Interaction of tyrosine kinase inhibitors with the human multidrug transporter proteins, MDR1 and MRP1”. Biochim. Biophys. Acta 1587 (2–3): 318–25. PMID 12084474. 
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  • Fromm MF (2003). „The influence of MDR1 polymorphisms on P-glycoprotein expression and function in humans”. Adv. Drug Deliv. Rev. 54 (10): 1295–310. DOI:10.1016/S0169-409X(02)00064-9. PMID 12406646. 
  • Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Michael M. Gottesman (2003). „P-glycoprotein: from genomics to mechanism”. Oncogene 22 (47): 7468–85. DOI:10.1038/sj.onc.1206948. PMID 14576852. 
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  • Ishikawa T, Onishi Y, Hirano H, et al. (2005). „Pharmacogenomics of drug transporters: a new approach to functional analysis of the genetic polymorphisms of ABCB1 (P-glycoprotein/MDR1)”. Biol. Pharm. Bull. 27 (7): 939–48. DOI:10.1248/bpb.27.939. PMID 15256718. 
  • Lee W, Lockhart AC, Kim RB, Rothenberg ML (2005). „Cancer pharmacogenomics: powerful tools in cancer chemotherapy and drug development”. Oncologist 10 (2): 104–11. DOI:10.1634/theoncologist.10-2-104. PMID 15709212. 
  • Gambrelle J, Labialle S, Dayan G, et al. (2005). „[Multidrug resistance in uveal melanoma.]”. Journal français d'ophtalmologie 28 (6): 652–9. PMID 16141933. 
  • Al-Shawi MK, Omote H (2006). „The Remarkable Transport Mechanism of P-glycoprotein; a Multidrug Transporter”. J. Bioenerg. Biomembr. 37 (6): 489–96. DOI:10.1007/s10863-005-9497-5. PMC 1459968. PMID 16691488. 
  • Orlowski S, Martin S, Escargueil A (2006). „P-glycoprotein and 'lipid rafts': some ambiguous mutual relationships (floating on them, building them or meeting them by chance?)”. Cell. Mol. Life Sci. 63 (9): 1038–59. DOI:10.1007/s00018-005-5554-9. PMID 16721513. 
  • Annese V, Valvano MR, Palmieri O, et al. (2006). „Multidrug resistance 1 gene in inflammatory bowel disease: a meta-analysis”. World J. Gastroenterol. 12 (23): 3636–44. PMID 16773678. 
  • Sekine I, Minna JD, Nishio K, et al. (2007). „A literature review of molecular markers predictive of clinical response to cytotoxic chemotherapy in patients with lung cancer”. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 1 (1): 31–7. PMID 17409824. 
  • Kumar YS, Adukondalu D, Sathish D, Vishnu YV, Ramesh G, Latha AB, Reddy PC, Sarangapani M, Rao YM (2010). „P-Glycoprotein- and cytochrome P-450-mediated herbal drug interactions”. Drug Metabol Drug Interact 25 (1-4): 3–16. DOI:10.1515/DMDI.2010.006. PMID 21417789. 

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