{PDOC00616}
{PS00766; THF_DHG_CYH_1}
{PS00767; THF_DHG_CYH_2}
{BEGIN}
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* Tetrahydrofolate dehydrogenase/cyclohydrolase signatures *
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Enzymes that participate in the transfer of  one-carbon  units are involved in
various biosynthetic pathways. In many of  these  processes  the  transfers of
one-carbon units are mediated by the coenzyme  tetrahydrofolate (THF). Various
reactions generate one-carbon derivatives of THF  which can be  interconverted
between   different  oxidation  states  by  formyltetrahydrofolate  synthetase
(EC 6.3.4.3),   methylenetetrahydrofolate   dehydrogenase   (EC   1.5.1.5   or
EC 1.5.1.15) and methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9).

The dehydrogenase and cyclohydrolase activities are expressed  by a variety of
multifunctional enzymes:

 - Eukaryotic C-1-tetrahydrofolate synthase (C1-THF synthase), which catalyzes
   all three reactions  described above.  Two  forms  of C1-THF synthases  are
   known [1],  one  is  located in the mitochondrial matrix,  while the second
   one is cytoplasmic. In  both forms the  dehydrogenase/cyclohydrolase domain
   is located in the N-terminal  section  of  the 900 amino acids protein  and
   consists of about 300 amino acid residues.  The  C1-THF synthases are NADP-
   dependent.
 - Eukaryotic  mitochondrial  bifunctional  dehydrogenase/cyclohydrolase  [2].
   This is  an  homodimeric  NAD-dependent  enzyme  of  about  300  amino acid
   residues.
 - Bacterial  folD  [3].  FolD  is  an homodimeric bifunctional NADP-dependent
   enzyme of about 290 amino acid residues.

The sequence of the dehydrogenase/cyclohydrolase  domain  is highly  conserved
in all forms of the enzyme.   As signature patterns  we selected two conserved
regions.  The first one is located in the N-terminal part of these enzymes and
contains three  acidic  residues.   The second pattern  is  a highly conserved
sequence of 9 amino acids which is located in the C-terminal section.

-Consensus pattern: [EQLT]-x-[EQKDS]-[LIVM](2)-x(2)-[LIVM]-x(2)-[LIVMY]-N-x-
                    [DNS]-x(5)-[LIVMF](3)-Q-[LM]-P-[LVI]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Consensus pattern: P-[GK]-G-[VI]-G-P-[MFI]-T-[IVA]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: December 2004 / Patterns and text revised.

[ 1] Shannon K.W., Rabinowitz J.C.
     "Isolation and characterization of the Saccharomyces cerevisiae MIS1
     gene encoding mitochondrial C1-tetrahydrofolate synthase."
     J. Biol. Chem. 263:7717-7725(1988).
     PubMed=2836393
[ 2] Belanger C., MacKenzie R.E.
     "Isolation and characterization of cDNA clones encoding the murine
     NAD-dependent methylenetetrahydrofolate
     dehydrogenase-methenyltetrahydrofolate cyclohydrolase."
     J. Biol. Chem. 264:4837-4843(1989).
     PubMed=2647744
[ 3] d'Ari L., Rabinowitz J.C.
     J. Biol. Chem. 266:23953-23958(1991).

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