Cys/Met metabolism PLP-dependent enzyme family

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Cys_Met_Meta_PP
PDB 2fq6 EBI.jpg
cystathionine beta-lyase (cbl) from escherichia coli in complex with n-hydrazinocarbonylmethyl-2-trifluoromethyl-benzamide
Identifiers
Symbol Cys_Met_Meta_PP
Pfam PF01053
Pfam clan CL0061
InterPro IPR000277
PROSITE PDOC00677
SCOP 1cs1
SUPERFAMILY 1cs1
CDD cd00614

In molecular biology, the Cys/Met metabolism PLP-dependent enzyme family is a family of proteins including enzymes involved in cysteine and methionine metabolism which use PLP (pyridoxal-5'-phosphate) as a cofactor.[1]

PLP is employed as it binds to amino groups and stabilises carbanion intermediates. PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the epsilon-amino group of an active site lysine residue on the enzyme. The alpha-amino group of the substrate displaces the lysine epsilon-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic.[2]

PLP is the active form of vitamin B6 (pyridoxine or pyridoxal). PLP is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination.[3][4][5]

A number of pyridoxal-dependent enzymes involved in the metabolism of cysteine, homocysteine and methionine have been shown to be evolutionary related.[1] These enzymes are tetrameric proteins of about 400 amino-acid residues. Each monomer has an active site, which however requires the N-terminal of another monomer to be completed (salt bridges to phosphate and entrance way). The phosphopyridoxyl group is attached to a lysine residue located in the central section of these enzymes and is stabilised by π-stacking interactions with a tyrosine residue above it.[6]

members[edit]

There are five different structurally related types of PLP enzymes. Members of this family belong to the type I and are:[1]

  • in the transsulfurylation route for methionine biosynthesis:
    • Cystathionine γ-synthase (metB) which joins an activated homoserine ether (acetyl or succinyl) with cysteine to form cystathionine
    • Cystathionine β-lyase (metC) which splits cystathionine into homocysteine and a deaminated alanine (pyruvate and ammonia)
  • in the direct sulfurylation pathway for methionine biosynthesis:
    • O-acetyl homoserine sulfhydrylase (metY) which adds a thiol group to an activated homoserine ether
    • O-succinylhomoserine sulfhydrylase (metZ) which adds a thiol group to an activated homoserine ether
  • in the reverse transsulfurylation pathway for cysteine biosynthesis:
    • Cystathionine γ-lyase (no common gene name) which joins an activated serine ether (acetyl or succinyl) with homocysteine to form cystathionine
    • Not Cystathionine β-synthase which is a PLP enzyme type II
  • cysteine biosynthesis from serine:
    • O-acetyl serine sulfhydrylase (cysK or cysM) which adds a thiol group to an activated serine ether
  • methionine degradation:
  • Methionine gamma-lyase (mdeA) which breaks down methionine at the thioether and amine bounds

Note: MetC, metB, metZ are closely related and have fuzzy boundaries so fall under the same NCBI orthologue cluster (COG0626).[1]

References[edit]

  1. ^ a b c d Ferla, M. P.; Patrick, W. M. (2014). "Bacterial methionine biosynthesis". Microbiology 160 (Pt 8): 1571–84. doi:10.1099/mic.0.077826-0. PMID 24939187.  edit
  2. ^ Toney MD (January 2005). "Reaction specificity in pyridoxal phosphate enzymes". Arch. Biochem. Biophys. 433 (1): 279–87. doi:10.1016/j.abb.2004.09.037. PMID 15581583. 
  3. ^ Hayashi H (September 1995). "Pyridoxal enzymes: mechanistic diversity and uniformity". J. Biochem. 118 (3): 463–73. PMID 8690703. 
  4. ^ John RA (April 1995). "Pyridoxal phosphate-dependent enzymes". Biochim. Biophys. Acta 1248 (2): 81–96. PMID 7748903. 
  5. ^ Eliot AC, Kirsch JF (2004). "Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations". Annu. Rev. Biochem. 73: 383–415. doi:10.1146/annurev.biochem.73.011303.074021. PMID 15189147. 
  6. ^ Aitken, S. M.; Lodha, P. H.; Morneau, D. J. K. (2011). "The enzymes of the transsulfuration pathways: Active-site characterizations". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 1814 (11): 1511. doi:10.1016/j.bbapap.2011.03.006.  edit

This article incorporates text from the public domain Pfam and InterPro IPR000277