{PDOC51826}
{PS51826; PSBD}
{BEGIN}
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* Peripheral subunit-binding (PSBD) domain profile *
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The ubiquitous 2-oxoacid dehydrogenases are a family of very large multienzyme
complexes consisting  of  multiple  copies  of  at  least  three enzymes which
catalyze the   oxidative  decarboxylation  of  several  different  2-oxoacids,
resulting in  acyl-CoA  products.  Members  of  this  family  include pyruvate
dehydrogenase (PDH), 2-oxoglutarate dehydrogenase (OGDH) and branched-chain 2-
oxoacid dehydrogenase  (BCDH).  The  three  enzymes  assembling  to form these
complexes are  the  decarboxylase E1 (called E1p, E1o and E1b in PDH, OGDH and
BCDH, respectively),  dihydrolipoamide  acetyl,  succinyl  and  branched-chain
transferase E2   (E2p,   E2o   and  E2b,  respectively)  and  dihydrolipoamide
dehydrogenase E3.  The  E3 component is identical in all three complexes (PDH,
OGDH and  BCDH) and catalyzes the same reaction. The structural core of all 2-
oxoacid dehydrogenase  complexes  (ODHc)  is  formed  of multiple copies of E2
subunits, with the E1 and E3 subunits bound on the periphery. The E2 component
of the ODHc’s of both bacteria and eukaryotes serves as the structural core of
these multienzyme  complexes  and  is  comprised  of  three  types of domains.
Starting with  the  N-terminus,  there  are 1–3 tandem repeated lipoyl domains
(LD) (see <PDOC50968>), followed by a peripheral subunit-binding domain (PSBD)
responsible for  binding  E1/E3  chains.  The  third  domain is the C-terminal
catalytic domain  (CD). The individual domains are separated by long, flexible
linker regions  allowing  large  movements  of  the lipoyl domain(s) to enable
active site   coupling.  The  PSBD  domain  binds  E1  or  E3,  but  not  both
simultaneously. The  flexible  linker  allows the PSBD domain (associated with
either E1  or  E3)  to  move  quite  freely with respect to the core formed E2
catalytic domains [1,2,3,4,5].

The ~35-residue  PSBD  domain has a compact structure consisting of two short,
parallel alpha-helices  (H1 and H2) separated by a loop (L1), a single helical
turn, and  a further, less well-ordered loop (L2) (see PDB:1BAL>). The compact
structure of the PSBD domain is stabilized mainly by hydrophobic interactions.
The interactions  between  the  PSBD domain and E3 are all mediated by charged
side chains,  forming  an  'electrostatic  zipper'.  The  residues of the PSBD
domain involved  in  the  interactions  are  all  provided by helix H1 of this
domain. Helix  H2  of  PSBD  does not interact with E3, but may be involved in
binding E1 [1,2,4].

The profile we developed covers the entire PSBD domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: January 2017 / First entry.

[ 1] Robien M.A., Clore G.M., Omichinski J.G., Perham R.N., Appella E.,
     Sakaguchi K., Gronenborn A.M.
     "Three-dimensional solution structure of the E3-binding domain of the
     dihydrolipoamide succinyltransferase core from the 2-oxoglutarate
     dehydrogenase multienzyme complex of Escherichia coli."
     Biochemistry 31:3463-3471(1992).
     PubMed=1554728
[ 2] Mande S.S., Sarfaty S., Allen M.D., Perham R.N., Hol W.G.J.
     "Protein-protein interactions in the pyruvate dehydrogenase
     multienzyme complex: dihydrolipoamide dehydrogenase complexed with the
     binding domain of dihydrolipoamide acetyltransferase."
     Structure 4:277-286(1996).
     PubMed=8805537
[ 3] Perham R.N.
     "Swinging arms and swinging domains in multifunctional enzymes:
     catalytic machines for multistep reactions."
     Annu. Rev. Biochem. 69:961-1004(2000).
     PubMed=10966480; DOI=10.1146/annurev.biochem.69.1.961
[ 4] Brautigam C.A., Wynn R.M., Chuang J.L., Machius M., Tomchick D.R.,
     Chuang D.T.
     "Structural insight into interactions between dihydrolipoamide
     dehydrogenase (E3)  and E3 binding protein of human pyruvate
     dehydrogenase complex."
     Structure 14:611-621(2006).
     PubMed=16442803; DOI=10.1016/j.str.2006.01.001
[ 5] Kumaran S., Patel M.S., Jordan F.
     "Nuclear magnetic resonance approaches in the study of 2-oxo acid
     dehydrogenase multienzyme complexes--a literature review."
     Molecules 18:11873-11903(2013).
     PubMed=24077172; DOI=10.3390/molecules181011873

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