BCKDHB
Mitohondrijska podjedinica beta 2-oksoizovalerat-dehidrogenaze jest enzim koji je kod ljudi kodiran genom BCKDHB.[5]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 392 aminokiseline, а molekulska težina 43 122 Da.[6]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MAVVAAAAGW | LLRLRAAGAE | GHWRRLPGAG | LARGFLHPAA | TVEDAAQRRQ | ||||
| VAHFTFQPDP | EPREYGQTQK | MNLFQSVTSA | LDNSLAKDPT | AVIFGEDVAF | ||||
| GGVFRCTVGL | RDKYGKDRVF | NTPLCEQGIV | GFGIGIAVTG | ATAIAEIQFA | ||||
| DYIFPAFDQI | VNEAAKYRYR | SGDLFNCGSL | TIRSPWGCVG | HGALYHSQSP | ||||
| EAFFAHCPGI | KVVIPRSPFQ | AKGLLLSCIE | DKNPCIFFEP | KILYRAAAEE | ||||
| VPIEPYNIPL | SQAEVIQEGS | DVTLVAWGTQ | VHVIREVASM | AKEKLGVSCE | ||||
| VIDLRTIIPW | DVDTICKSVI | KTGRLLISHE | APLTGGFASE | ISSTVQEECF | ||||
| LNLEAPISRV | CGYDTPFPHI | FEPFYIPDKW | KCYDALRKMI | NY |
Funkcija
urediDehidrogenaza keto kiseline s razgranatim lancem je multienzimski kompleks povezan sa unutrašnjom mitohondrijskom membranom, a funkcionira u katabolizmu aminokiselina razgranatog lanca. Kompleks se sastoji od više kopija tri komponente: dekarboksilaze razgranatog lanca alfa-keto kiseline (E1), lipoamid aciltransferaze (E2) i lipoamid dehidrogenaze (E3). Ovaj gen kodira podjedinicu E1 beta, a njegove mutacije su povezane s bolest mokraće s mirisom javorovog sirupa (MSUD), tip 1B. Alternativna prerada na ovom mjestu rezultira varijantama transkripta s tri različita nekodirajuća područja, ali kodiraju iste izoforme.[5]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000083123 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032263 - 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 "Entrez Gene: BCKDHB branched chain keto acid dehydrogenase E1, beta polypeptide (maple syrup urine disease)".
- ^ "UniProt, P21953" (jezik: engleski). Pristupljeno 6. 10. 2021.
Dopunska literatura
uredi- Popov KM, Zhao Y, Shimomura Y, et al. (1992). "Branched-chain alpha-ketoacid dehydrogenase kinase. Molecular cloning, expression, and sequence similarity with histidine protein kinases". J. Biol. Chem. 267 (19): 13127–30. doi:10.1016/S0021-9258(18)42179-5. PMID 1377677.
- Mitsubuchi H, Nobukuni Y, Endo F, Matsuda I (1991). "Structural organization and chromosomal localization of the gene for the E1 beta subunit of human branched chain alpha-keto acid dehydrogenase". J. Biol. Chem. 266 (22): 14686–91. doi:10.1016/S0021-9258(18)98740-5. PMID 1860867.
- Zneimer SM, Lau KS, Eddy RL, et al. (1991). "Regional assignment of two genes of the human branched-chain alpha-keto acid dehydrogenase complex: the E1 beta gene (BCKDHB) to chromosome 6p21-22 and the E2 gene (DBT) to chromosome 1p31". Genomics. 10 (3): 740–7. doi:10.1016/0888-7543(91)90458-Q. PMID 1889817.
- Nobukuni Y, Mitsubuchi H, Akaboshi I, et al. (1991). "Maple syrup urine disease. Complete defect of the E1 beta subunit of the branched chain alpha-ketoacid dehydrogenase complex due to a deletion of an 11-bp repeat sequence which encodes a mitochondrial targeting leader peptide in a family with the disease". J. Clin. Invest. 87 (5): 1862–6. doi:10.1172/JCI115209. PMC 295312. PMID 2022752.
- Chuang JL, Cox RP, Chuang DT (1990). "Molecular cloning of the mature E1b-beta subunit of human branched-chain alpha-keto acid dehydrogenase complex". FEBS Lett. 262 (2): 305–9. doi:10.1016/0014-5793(90)80215-5. PMID 2335211. S2CID 84069883.
- Nobukuni Y, Mitsubuchi H, Endo F, et al. (1990). "Maple syrup urine disease. Complete primary structure of the E1 beta subunit of human branched chain alpha-ketoacid dehydrogenase complex deduced from the nucleotide sequence and a gene analysis of patients with this disease". J. Clin. Invest. 86 (1): 242–7. doi:10.1172/JCI114690. PMC 296713. PMID 2365818.
- Wynn RM, Kochi H, Cox RP, Chuang DT (1994). "Differential processing of human and rat E1 alpha precursors of the branched-chain alpha-keto acid dehydrogenase complex caused by an N-terminal proline in the rat sequence". Biochim. Biophys. Acta. 1201 (1): 125–8. doi:10.1016/0304-4165(94)90161-9. PMID 7918575.
- Nobukuni Y, Mitsubuchi H, Hayashida Y, et al. (1993). "Heterogeneity of mutations in maple syrup urine disease (MSUD): screening and identification of affected E1 alpha and E1 beta subunits of the branched-chain alpha-keto-acid dehydrogenase multienzyme complex". Biochim. Biophys. Acta. 1225 (1): 64–70. doi:10.1016/0925-4439(93)90123-i. PMID 8161368.
- Chuang JL, Cox RP, Chuang DT (1996). "Maple syrup urine disease: the E1beta gene of human branched-chain alpha-ketoacid dehydrogenase complex has 11 rather than 10 exons, and the 3' UTR in one of the two E1beta mRNAs arises from intronic sequences". Am. J. Hum. Genet. 58 (6): 1373–7. PMC 1915070. PMID 8651316.
- Edelmann L, Wasserstein MP, Kornreich R, et al. (2001). "Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population". Am. J. Hum. Genet. 69 (4): 863–8. doi:10.1086/323677. PMC 1226071. PMID 11509994.
- Chang CF, Chou HT, Chuang JL, et al. (2002). "Solution structure and dynamics of the lipoic acid-bearing domain of human mitochondrial branched-chain alpha-keto acid dehydrogenase complex". J. Biol. Chem. 277 (18): 15865–73. doi:10.1074/jbc.M110952200. PMID 11839747.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. USA. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Wynn RM, Machius M, Chuang JL, et al. (2003). "Roles of His291-alpha and His146-beta' in the reductive acylation reaction catalyzed by human branched-chain alpha-ketoacid dehydrogenase: refined phosphorylation loop structure in the active site". J. Biol. Chem. 278 (44): 43402–10. doi:10.1074/jbc.M306204200. PMID 12902323.
- Li J, Wynn RM, Machius M, et al. (2004). "Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase". J. Biol. Chem. 279 (31): 32968–78. doi:10.1074/jbc.M403611200. PMID 15166214.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Machius M, Wynn RM, Chuang JL, et al. (2006). "A versatile conformational switch regulates reactivity in human branched-chain alpha-ketoacid dehydrogenase". Structure. 14 (2): 287–98. doi:10.1016/j.str.2005.10.009. PMID 16472748.
- Li J, Machius M, Chuang JL, et al. (2007). "The two active sites in human branched-chain alpha-keto acid dehydrogenase operate independently without an obligatory alternating-site mechanism". J. Biol. Chem. 282 (16): 11904–13. doi:10.1074/jbc.M610843200. PMID 17329260.
Vanjski linkovi
uredi- Lokacija ljudskog genoma BCKDHB i stranica sa detaljima o genu BCKDHB u UCSC Genome Browseru.
