P-glikoprotein
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]
| ATP-vezujuća kaseta, potfamilija B (MDR/TAP), član 1 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
 Kristalografska struktura MDR3 proteina miša. Približna 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 | |||||||||||
| Simboli | ABCB1; ABC20; CD243; CLCS; GP170; MDR1; P-GP; PGY1 | ||||||||||
| Vanjski ID | OMIM: 171050 MGI: 97570 HomoloGene: 55496 GeneCards: ABCB1 Gene | ||||||||||
| EC broj | 3.6.3.44 | ||||||||||
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| Pregled RNK izražavanja | |||||||||||
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| podaci | |||||||||||
| Ortolozi | |||||||||||
| Vrsta | Čovek | Miš | |||||||||
| Entrez | 5243 | 18671 | |||||||||
| Ensembl | ENSG00000085563 | ENSMUSG00000040584 | |||||||||
| UniProt | P08183 | P21447 | |||||||||
| RefSeq (mRNA) | NM_000927.4 | NM_011076.2 | |||||||||
| RefSeq (protein) | NP_000918.2 | NP_035206.2 | |||||||||
| Lokacija (UCSC) |
Chr 7: 87.13 - 87.34 Mb |
Chr 5: 8.66 - 8.75 Mb | |||||||||
| PubMed pretraga | [1] | [2] | |||||||||
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
уреди- ^ PDB: 3G60; Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G (2009). „Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding”. Science. 323 (5922): 1718—22. PMC 2720052
. PMID 19325113. doi:10.1126/science.1168750.
- ^ Ueda K; Clark DP; Chen CJ; Roninson IB; Michael M. Gottesman; Pastan I (1987). „The human multidrug resistance (mdr1) gene. cDNA cloning and transcription initiation”. J. Biol. Chem. 262 (2): 505—8. PMID 3027054. Архивирано из оригинала 26. 07. 2008. г. Приступљено 30. 08. 2012.
- ^ Dean, Michael (1. 11. 2002). „The Human ATP-Binding Cassette (ABC) Transporter Superfamily”. National Library of Medicine (US), NCBI. Архивирано из оригинала 12. 02. 2006. г. Приступљено 2. 3. 2008.
Literatura
уреди- Ling V (1997). „Multidrug resistance: molecular mechanisms and clinical relevance”. Cancer Chemother. Pharmacol. 40 Suppl (7): S3—8. PMID 9272126. doi:10.1007/s002800051053.
- 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. PMID 11258197. doi:10.1517/14622416.2.1.51.
- 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. ISBN 978-0-470-84635-3. PMID 11990778. doi:10.1002/0470846356.ch15.
- 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. ISBN 978-0-470-84635-3. PMID 11990782. doi:10.1002/0470846356.ch5.
- 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.
- Pallis M, Turzanski J, Higashi Y, Russell N (2003). „P-glycoprotein in acute myeloid leukaemia: therapeutic implications of its association with both a multidrug-resistant and an apoptosis-resistant phenotype”. Leuk. Lymphoma. 43 (6): 1221—8. PMID 12152989. doi:10.1080/10428190290026277.
- Schaich M, Illmer T (2003). „Mdr1 gene expression and mutations in Ras proto-oncogenes in acute myeloid leukemia”. Leuk. Lymphoma. 43 (7): 1345—54. PMID 12389613. doi:10.1080/10428190290033279.
- Fromm MF (2003). „The influence of MDR1 polymorphisms on P-glycoprotein expression and function in humans”. Adv. Drug Deliv. Rev. 54 (10): 1295—310. PMID 12406646. doi:10.1016/S0169-409X(02)00064-9.
- Ambudkar SV; Kimchi-Sarfaty C; Sauna ZE; Michael M. Gottesman (2003). „P-glycoprotein: from genomics to mechanism”. Oncogene. 22 (47): 7468—85. PMID 14576852. doi:10.1038/sj.onc.1206948.
- Jamroziak K, Robak T (2004). „Pharmacogenomics of MDR1/ABCB1 gene: the influence on risk and clinical outcome of haematological malignancies”. Hematology. 9 (2): 91—105. PMID 15203864. doi:10.1080/10245330310001638974.
- 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. PMID 15256718. doi:10.1248/bpb.27.939.
- Lee W, Lockhart AC, Kim RB, Rothenberg ML (2005). „Cancer pharmacogenomics: powerful tools in cancer chemotherapy and drug development”. Oncologist. 10 (2): 104—11. PMID 15709212. doi:10.1634/theoncologist.10-2-104.
- 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. PMC 1459968 . PMID 16691488. doi:10.1007/s10863-005-9497-5.
- 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. PMID 16721513. doi:10.1007/s00018-005-5554-9.
- 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. PMID 21417789. doi:10.1515/DMDI.2010.006.
Spoljašnje veze
уреди- P-Glycoprotein на US National Library of Medicine Medical Subject Headings (MeSH)
- Jessica R Oesterheld (1. 5. 2002). „P-glycoprotein”. Mental Health Connections, Inc. Архивирано из оригинала 7. 2. 2008. г. Приступљено 2. 3. 2008.
- P-glycoprotein substrate prediction