1olx

Structural highlights

Disease

ODBA_HUMAN Defects in BCKDHA are a cause of maple syrup urine disease type IA (MSUD1A) [MIM:248600. MSUD is an autosomal recessive disorder characterized by mental and physical retardation, feeding problems, and a maple syrup odor to the urine.^{[1] [2] [3] [4] [5] [6] [7] [8]}

Function

ODBA_HUMAN The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• 2-oxoisovalerate dehydrogenase 3D structures

References

1. ↑ Dariush N, Fisher CW, Cox RP, Chuang DT. Structure of the gene encoding the entire mature E1 alpha subunit of human branched-chain alpha-keto acid dehydrogenase complex. FEBS Lett. 1991 Jun 17;284(1):34-8. PMID:2060625
2. ↑ Chuang JL, Fisher CR, Cox RP, Chuang DT. Molecular basis of maple syrup urine disease: novel mutations at the E1 alpha locus that impair E1(alpha 2 beta 2) assembly or decrease steady-state E1 alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex. Am J Hum Genet. 1994 Aug;55(2):297-304. PMID:8037208
3. ↑ Zhang B, Edenberg HJ, Crabb DW, Harris RA. Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease. J Clin Invest. 1989 Apr;83(4):1425-9. PMID:2703538 doi:http://dx.doi.org/10.1172/JCI114033
4. ↑ Matsuda I, Nobukuni Y, Mitsubuchi H, Indo Y, Endo F, Asaka J, Harada A. A T-to-A substitution in the E1 alpha subunit gene of the branched-chain alpha-ketoacid dehydrogenase complex in two cell lines derived from Menonite maple syrup urine disease patients. Biochem Biophys Res Commun. 1990 Oct 30;172(2):646-51. PMID:2241958
5. ↑ Fisher CR, Fisher CW, Chuang DT, Cox RP. Occurrence of a Tyr393----Asn (Y393N) mutation in the E1 alpha gene of the branched-chain alpha-keto acid dehydrogenase complex in maple syrup urine disease patients from a Mennonite population. Am J Hum Genet. 1991 Aug;49(2):429-34. PMID:1867199
6. ↑ Fisher CR, Chuang JL, Cox RP, Fisher CW, Star RA, Chuang DT. Maple syrup urine disease in Mennonites. Evidence that the Y393N mutation in E1 alpha impedes assembly of the E1 component of branched-chain alpha-keto acid dehydrogenase complex. J Clin Invest. 1991 Sep;88(3):1034-7. PMID:1885764 doi:http://dx.doi.org/10.1172/JCI115363
7. ↑ Nobukuni Y, Mitsubuchi H, Hayashida Y, Ohta K, Indo Y, Ichiba Y, Endo F, Matsuda I. 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. 1993 Nov 25;1225(1):64-70. PMID:8161368
8. ↑ Chuang JL, Davie JR, Chinsky JM, Wynn RM, Cox RP, Chuang DT. Molecular and biochemical basis of intermediate maple syrup urine disease. Occurrence of homozygous G245R and F364C mutations at the E1 alpha locus of Hispanic-Mexican patients. J Clin Invest. 1995 Mar;95(3):954-63. PMID:7883996 doi:http://dx.doi.org/10.1172/JCI117804
9. ↑ Wynn RM, Machius M, Chuang JL, Li J, Tomchick DR, Chuang DT. 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. 2003 Oct 31;278(44):43402-10. Epub 2003 Aug 5. PMID:12902323 doi:http://dx.doi.org/10.1074/jbc.M306204200