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MetaCyc Enzyme: bifunctional β-cystathionase, PLP-dependent and regulator of maltose regulon

Gene: malY Accession Numbers: EG10564 (MetaCyc), b1622, ECK1617

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of bifunctional β-cystathionase, PLP-dependent and regulator of maltose regulon = [MalY]2
         bifunctional β-cystathionase, PLP-dependent and regulator of maltose regulon = MalY

Summary:
MalY is a bifunctional protein with a regulatory as well as an enzymatic function [Reidl91, Zdych95].

MalY acts as a negative regulator of the maltose regulon by interacting directly with the MalT transcriptional activator and competing with the inducer maltotriose [Schreiber00, Clausen00]. Mutations that reduce MalY's repressor activity map to regions away from the enzyme active site [Clausen00]. Mutations in MalT have differential effects on its sensitivity to Aes, MalY and MalK, which inhibit the activator in similar, yet distinct, ways [Joly02, Schlegel02a, Joly04].

MalY belongs to a family of aminotransferases [Mehta93] and catalyzes the carbon-sulfur bond cleavage (β C-S lyase) of cystathionine [Zdych95]. The cystathionase activity of MalY is not required for its regulatory function [Zdych95]. The physiological substrate is unknown [Clausen00]. An in-gel staining assay showed that MalY also has cysteine desulfhydrase (CD) activity. A quintuple ΔmetC tnaA cysK cysM malY mutant contains significantly reduced CD activity [Awano05].

Crystal structures of the wild-type and a mutant enzyme have been solved. The PLP cofactor is bound to Lys233 [Clausen00]. PLP binding increases the stability of the dimeric enzyme [Bertoldi05].

Overexpression of malY in an otherwise wild type strain interferes with growth on maltose [Reidl91]. Overexpression in a metC mutant complements the methionine requirement of the mutant [Zdych95].

Reviews: [Schlegel02, Commichau08]

Citations: [Decker98, DAmbrosio08, Reimann09]

Locations: cytosol

Map Position: [1,698,981 -> 1,700,153]

Molecular Weight of Polypeptide: 43.642 kD (from nucleotide sequence), 42.0 kD (experimental) [Reidl91 ]

Molecular Weight of Multimer: 90.0 kD (experimental) [Bertoldi05]

Unification Links: ASAP:ABE-0005432 , CGSC:32257 , DIP:DIP-10151N , EchoBASE:EB0559 , EcoGene:EG10564 , EcoliWiki:b1622 , ModBase:P23256 , OU-Microarray:b1622 , PortEco:malY , PR:PRO_000023157 , Pride:P23256 , Protein Model Portal:P23256 , RefSeq:NP_416139 , RegulonDB:EG10564 , SMR:P23256 , String:511145.b1622 , UniProt:P23256

Relationship Links: InterPro:IN-FAMILY:IPR004839 , InterPro:IN-FAMILY:IPR015421 , InterPro:IN-FAMILY:IPR015422 , InterPro:IN-FAMILY:IPR015424 , InterPro:IN-FAMILY:IPR027619 , PDB:Structure:1D2F , Pfam:IN-FAMILY:PF00155 , Prosite:IN-FAMILY:PS00599

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0043433 - negative regulation of sequence-specific DNA binding transcription factor activity Inferred from experiment [Schreiber00]
GO:0006351 - transcription, DNA-templated Inferred by computational analysis [UniProtGOA11]
GO:0006355 - regulation of transcription, DNA-templated Inferred by computational analysis [UniProtGOA11]
GO:0008652 - cellular amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11]
GO:0009058 - biosynthetic process Inferred by computational analysis [GOA01]
GO:0009086 - methionine biosynthetic process Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0004121 - cystathionine beta-lyase activity Inferred from experiment Inferred by computational analysis [GOA01a, Zdych95]
GO:0005515 - protein binding Inferred from experiment [Clausen00]
GO:0030170 - pyridoxal phosphate binding Inferred from experiment Inferred by computational analysis [GOA01, Zdych95, Clausen00]
GO:0042803 - protein homodimerization activity Inferred from experiment [Bertoldi05]
GO:0080146 - L-cysteine desulfhydrase activity Inferred from experiment [Awano05]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism carbon utilization carbon compounds
regulation genetic unit regulated operon
regulation type of regulation posttranscriptional inhibition / activation of enzymes

Credits:
Created in EcoCyc 31-Oct-2013 by Keseler I , SRI International
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: cystathionine β-lyase (bifunctional β-cystathionase, PLP-dependent and regulator of maltose regulon)

Synonyms: β-cystathionase, cystathionase

L-cystathionine <=> 2-aminoprop-2-enoate + L-homocysteine + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

Alternative Substrates for L-cystathionine: L-cystine [Zdych95 ] , S-(2-aminoethyl)-L-cysteine [Zdych95 ] , lanthionine [Zdych95 ]

In Pathways: superpathway of S-adenosyl-L-methionine biosynthesis , aspartate superpathway , superpathway of lysine, threonine and methionine biosynthesis I , superpathway of methionine biosynthesis (transsulfuration) , homoserine and methionine biosynthesis , methionine biosynthesis I

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Cofactors or Prosthetic Groups: pyridoxal 5'-phosphate [Zdych95]

Kinetic Parameters:

Substrate
Km (μM)
Citations
L-cystine
1700.0
[Zdych95]

pH(opt): 8.2 [Zdych95]


Enzymatic reaction of: L-cysteine desulfhydrase (bifunctional β-cystathionase, PLP-dependent and regulator of maltose regulon)

L-cysteine <=> 2-aminoprop-2-enoate + hydrogen sulfide + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

In Pathways: L-cysteine degradation II

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Sequence Features

Feature Class Location Citations Comment
N6-pyridoxal-phosphate-Lys-Modification 233
[UniProt11]
UniProt: N6-(pyridoxal phosphate)lysine.
Mutagenesis-Variant 233
[Zdych95, UniProt11a]
Alternate sequence: I; UniProt: Loss of enzymatic activity; but no loss of repression function.

History:
10/20/97 Gene b1622 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10564; confirmed by SwissProt match.


References

Awano05: Awano N, Wada M, Mori H, Nakamori S, Takagi H (2005). "Identification and functional analysis of Escherichia coli cysteine desulfhydrases." Appl Environ Microbiol 71(7);4149-52. PMID: 16000837

Bertoldi05: Bertoldi M, Cellini B, Laurents DV, Borri Voltattorni C (2005). "Folding pathway of the pyridoxal 5'-phosphate C-S lyase MalY from Escherichia coli." Biochem J 389(Pt 3);885-98. PMID: 15823094

Clausen00: Clausen T, Schlegel A, Peist R, Schneider E, Steegborn C, Chang YS, Haase A, Bourenkov GP, Bartunik HD, Boos W (2000). "X-ray structure of MalY from Escherichia coli: a pyridoxal 5'-phosphate-dependent enzyme acting as a modulator in mal gene expression." EMBO J 19(5);831-42. PMID: 10698925

Commichau08: Commichau FM, Stulke J (2008). "Trigger enzymes: bifunctional proteins active in metabolism and in controlling gene expression." Mol Microbiol 67(4);692-702. PMID: 18086213

DAmbrosio08: D'Ambrosio C, Mandrich L, Rossi M, Scaloni A, Manco G (2008). "A proteomic approach to study Escherichia coli. Acetyl esterase interactors unveil a sequence motif involved in protein-protein interaction." Protein Pept Lett 15(4);333-40. PMID: 18473943

Decker98: Decker K, Plumbridge J, Boos W (1998). "Negative transcriptional regulation of a positive regulator: the expression of malT, encoding the transcriptional activator of the maltose regulon of Escherichia coli, is negatively controlled by Mlc." Mol Microbiol 27(2);381-90. PMID: 9484893

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

Joly02: Joly N, Danot O, Schlegel A, Boos W, Richet E (2002). "The Aes protein directly controls the activity of MalT, the central transcriptional activator of the Escherichia coli maltose regulon." J Biol Chem 277(19);16606-13. PMID: 11867639

Joly04: Joly N, Bohm A, Boos W, Richet E (2004). "MalK, the ATP-binding cassette component of the Escherichia coli maltodextrin transporter, inhibits the transcriptional activator malt by antagonizing inducer binding." J Biol Chem 279(32);33123-30. PMID: 15180985

Mehta93: Mehta PK, Christen P (1993). "Homology of pyridoxal-5'-phosphate-dependent aminotransferases with the cobC (cobalamin synthesis), nifS (nitrogen fixation), pabC (p-aminobenzoate synthesis) and malY (abolishing endogenous induction of the maltose system) gene products." Eur J Biochem 211(1-2);373-6. PMID: 8425548

Reidl91: Reidl J, Boos W (1991). "The malX malY operon of Escherichia coli encodes a novel enzyme II of the phosphotransferase system recognizing glucose and maltose and an enzyme abolishing the endogenous induction of the maltose system." J Bacteriol 173(15);4862-76. PMID: 1856179

Reimann09: Reimann SA, Wolfe AJ (2009). "A critical process controlled by MalT and OmpR is revealed through synthetic lethality." J Bacteriol 191(16);5320-4. PMID: 19502392

Schlegel02: Schlegel A, Bohm A, Lee SJ, Peist R, Decker K, Boos W (2002). "Network regulation of the Escherichia coli maltose system." J Mol Microbiol Biotechnol 4(3);301-7. PMID: 11931562

Schlegel02a: Schlegel A, Danot O, Richet E, Ferenci T, Boos W (2002). "The N terminus of the Escherichia coli transcription activator MalT is the domain of interaction with MalY." J Bacteriol 184(11);3069-77. PMID: 12003949

Schreiber00: Schreiber V, Steegborn C, Clausen T, Boos W, Richet E (2000). "A new mechanism for the control of a prokaryotic transcriptional regulator: antagonistic binding of positive and negative effectors." Mol Microbiol 35(4);765-76. PMID: 10692154

UniProt11: UniProt Consortium (2011). "UniProt version 2011-11 released on 2011-11-22 00:00:00." Database.

UniProt11a: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Zdych95: Zdych E, Peist R, Reidl J, Boos W (1995). "MalY of Escherichia coli is an enzyme with the activity of a beta C-S lyase (cystathionase)." J Bacteriol 177(17);5035-9. PMID: 7665481


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Mon Nov 24, 2014, BIOCYC14B.