METB_HELPX
ID METB_HELPX Reviewed; 380 AA.
AC Q1M0P5;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 1.
DT 25-MAY-2022, entry version 57.
DE RecName: Full=Cystathionine gamma-synthase;
DE Short=CGS;
DE EC=2.5.1.48;
DE AltName: Full=O-succinylhomoserine (thiol)-lyase;
GN Name=metB;
OS Helicobacter pylori (Campylobacter pylori).
OC Bacteria; Proteobacteria; Epsilonproteobacteria; Campylobacterales;
OC Helicobacteraceae; Helicobacter.
OX NCBI_TaxID=210;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES,
RP ACTIVITY REGULATION, AND BIOTECHNOLOGY.
RC STRAIN=SS1;
RX PubMed=17981822; DOI=10.1093/jb/mvm194;
RA Kong Y., Wu D., Bai H., Han C., Chen J., Chen L., Hu L., Jiang H., Shen X.;
RT "Enzymatic characterization and inhibitor discovery of a new cystathionine
RT gamma-synthase from Helicobacter pylori.";
RL J. Biochem. 143:59-68(2008).
CC -!- FUNCTION: Catalyzes the formation of L-cystathionine from O-succinyl-L-
CC homoserine (OSHS) and L-cysteine, via a gamma-replacement reaction (By
CC similarity). In the absence of thiol, catalyzes gamma-elimination to
CC form 2-oxobutanoate, succinate and ammonia. {ECO:0000250,
CC ECO:0000269|PubMed:17981822}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-cysteine + O-succinyl-L-homoserine = H(+) + L,L-
CC cystathionine + succinate; Xref=Rhea:RHEA:20397, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:35235, ChEBI:CHEBI:57661,
CC ChEBI:CHEBI:58161; EC=2.5.1.48;
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250};
CC Note=Binds 1 pyridoxal phosphate per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Four natural products, alpha-lapachone, 9-hydroxy-
CC alpha-lapachone, Paulownin, and Yangambin, show strong inhibitory
CC activities against CGS. All these four inhibitors prevent the binding
CC of OSHS to CGS in a non-competitive fashion. These compounds are
CC specific inhibitors against CGS from H.pylori relative to E.coli since
CC they exhibit very low inhibition activities against CGS from E.coli.
CC {ECO:0000269|PubMed:17981822}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.02 mM for O-succinyl-L-homoserine (at pH 7.5 and 25 degrees
CC Celsius) {ECO:0000269|PubMed:17981822};
CC Note=The KM value was measured when assaying the gamma-elimination
CC reaction.;
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:17981822};
CC Temperature dependence:
CC Optimum temperature is 45 degrees Celsius.
CC {ECO:0000269|PubMed:17981822};
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-cystathionine from O-succinyl-L-homoserine: step 1/1.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- BIOTECHNOLOGY: CGS from H.pylori is an attractive target for
CC antibiotics discovery since the four natural inhibitors alpha-
CC lapachone, 9-hydroxy-alpha-lapachone, Paulownin, and Yangambin also
CC display strong antibacterial activity in vitro, highly inhibiting the
CC growth of H.pylori, whereas no antibacterial activity against E.coli in
CC vitro. These inhibitors might thus be used as potential lead compounds
CC for further research in the discovery of anti-H.pylori agents.
CC {ECO:0000269|PubMed:17981822}.
CC -!- SIMILARITY: Belongs to the trans-sulfuration enzymes family.
CC {ECO:0000305}.
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DR EMBL; AY904357; AAX99219.1; -; Genomic_DNA.
DR RefSeq; WP_077231658.1; NZ_AP017633.1.
DR AlphaFoldDB; Q1M0P5; -.
DR SMR; Q1M0P5; -.
DR STRING; 1345592.CBOM010000024_gene1403; -.
DR eggNOG; COG0626; Bacteria.
DR BRENDA; 2.5.1.48; 2604.
DR SABIO-RK; Q1M0P5; -.
DR UniPathway; UPA00051; UER00077.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003962; F:cystathionine gamma-synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0102028; F:cystathionine gamma-synthase activity (acts on O-phosphohomoserine); IEA:UniProtKB-EC.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0009086; P:methionine biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0019346; P:transsulfuration; IEA:InterPro.
DR CDD; cd00614; CGS_like; 1.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR000277; Cys/Met-Metab_PyrdxlP-dep_enz.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR PANTHER; PTHR11808; PTHR11808; 1.
DR Pfam; PF01053; Cys_Met_Meta_PP; 1.
DR PIRSF; PIRSF001434; CGS; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR PROSITE; PS00868; CYS_MET_METAB_PP; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Cytoplasm; Methionine biosynthesis;
KW Pyridoxal phosphate; Transferase.
FT CHAIN 1..380
FT /note="Cystathionine gamma-synthase"
FT /id="PRO_0000416405"
FT MOD_RES 195
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 380 AA; 41151 MW; DF76DC0C0801C756 CRC64;
MHMQTKLIHG GISEDATTGA VSVPIYQTST YRQDAIGHHK GYEYSRSGNP TRFALEELIA
DLEGGVKGFA FASGLAGIHA VFSLLQSGDH VLLGDDVYGG TFRLFNKVLV KNGLSCTIID
TSDLSQIKKA IKPNTKALYL ETPSNPLLKI TDLAQCASVA KDHGLLTIVD NTFATPYYQN
PLLLGADIVV HSGTKYLGGH SDVVAGLVTT NNEALAQEIA FFQNAIGGVL GPQDSWLLQR
GIKTLGLRMQ AHQKNALCVA EFLEKHPKVE RVYYPGLPTH PNYELAKKQM RGFSGMLSFT
LKNDSEATPF VESLKLFILG ESLGGVESLV GVPAFMTHAC IPKTQREAAG IRDGLVRLSV
GIEHEQDLLE DLEQAFAKIS
