{PDOC00168}
{PS00189; LIPOYL}
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* 2-oxo acid dehydrogenases acyltransferase component lipoyl binding site *
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The 2-oxo acid dehydrogenase  multienzyme complexes [1,2]  from  bacterial and
eukaryotic sources  catalyze  the  oxidative decarboxylation of 2-oxo acids to
the corresponding acyl-CoA.   The three members  of this family of multienzyme
complexes are:

 - Pyruvate dehydrogenase complex (PDC).
 - 2-oxoglutarate dehydrogenase complex (OGDC).
 - Branched-chain 2-oxo acid dehydrogenase complex (BCOADC).

These three  complexes  share  a  common  architecture:   they are composed of
multiple copies  of three component enzymes - E1, E2 and E3.  E1 is a thiamine
pyrophosphate-dependent  2-oxo  acid  dehydrogenase,  E2     a dihydrolipamide
acyltransferase, and E3 an FAD-containing dihydrolipamide dehydrogenase.

E2 acyltransferases   have  an  essential  cofactor,  lipoic  acid,  which  is
covalently bound  via  a amide linkage to a lysine group. The E2 components of
OGCD and BCOACD bind a single lipoyl group, while those of PDC bind either one
(in yeast  and in Bacillus), two (in mammals), or three (in Azotobacter and in
Escherichia coli) lipoyl groups [3].

In addition to  the E2 components of the three  enzymatic  complexes described
above, a lipoic acid cofactor is also found in the following proteins:

 - H-protein of the  glycine cleavage system (GCS) [4]. GCS  is  a multienzyme
   complex of  four  protein  components,  which  catalyzes the degradation of
   glycine. H  protein  shuttles  the  methylamine group of glycine from the P
   protein to  the  T protein. H-protein from either prokaryotes or eukaryotes
   binds a single lipoic group.
 - Mammalian and  yeast  pyruvate dehydrogenase complexes differ  from that of
   other sources, in that they contain, in small amounts, a protein of unknown
   function -  designated  protein  X  or component X. Its sequence is closely
   related to that of E2 subunits and seems to bind a lipoic group [5].
 - Fast migrating protein (FMP) (gene acoC)  from  Alcaligenes  eutrophus [6].
   This protein is most probably a dihydrolipamide acyltransferase involved in
   acetoin metabolism.

We developed  a  signature  pattern  which allows the detection of the lipoyl-
binding site.

-Consensus pattern: [GDN]-x(2)-[LIVF]-x(3)-{VH}-{M}-[LIVMFCA]-x(2)-[LIVMFA]-
                    {LDFY}-{KPE}-x-K-[GSTAIVW]-[STAIVQDN]-x(2)-[LIVMFS]-x(5)-
                    [GCN]-x-[LIVMFY]
                    [K is the lipoyl-binding site]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: 6.

-Note: The domain  around  the  lipoyl-binding  lysine residue is evolutionary
 related to that around the biotin-binding lysine  residue of biotin requiring
 enzymes (see <PDOC00167>).

-Last update: April 2006 / Pattern revised.

[ 1] Yeaman S.J.
     "The 2-oxo acid dehydrogenase complexes: recent advances."
     Biochem. J. 257:625-632(1989).
     PubMed=2649080
[ 2] Yeaman S.J.
     Trends Biochem. Sci. 11:293-296(1986).
[ 3] Russel G.C., Guest J.R.
     Biochim. Biophys. Acta 1076:225-232(1991).
[ 4] Fujiwara K., Okamura-Ikeda K., Motokawa Y.
     "Chicken liver H-protein, a component of the glycine cleavage system.
     Amino acid sequence and identification of the N epsilon-lipoyllysine
     residue."
     J. Biol. Chem. 261:8836-8841(1986).
     PubMed=3522581
[ 5] Behal R.H., Browning K.S., Hall T.B., Reed L.J.
     "Cloning and nucleotide sequence of the gene for protein X from
     Saccharomyces cerevisiae."
     Proc. Natl. Acad. Sci. U.S.A. 86:8732-8736(1989).
     PubMed=2682658
[ 6] Priefert H., Hein S., Kruger N., Zeh K., Schmidt B., Steinbuechel A.
     "Identification and molecular characterization of the Alcaligenes
     eutrophus H16 aco operon genes involved in acetoin catabolism."
     J. Bacteriol. 173:4056-4071(1991).
     PubMed=2061286

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