MSHC_MYCS2
ID MSHC_MYCS2 Reviewed; 412 AA.
AC A0QZY0; I7GD10;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=L-cysteine:1D-myo-inositol 2-amino-2-deoxy-alpha-D-glucopyranoside ligase;
DE Short=L-Cys:GlcN-Ins ligase;
DE EC=6.3.1.13;
DE AltName: Full=Mycothiol ligase;
DE Short=MSH ligase;
GN Name=mshC; Synonyms=cysS2; OrderedLocusNames=MSMEG_4189, MSMEI_4091;
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
RN [4]
RP PROTEIN SEQUENCE OF 1-20, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=12033919; DOI=10.1021/bi012212u;
RA Sareen D., Steffek M., Newton G.L., Fahey R.C.;
RT "ATP-dependent L-cysteine:1D-myo-inosityl 2-amino-2-deoxy-alpha-D-
RT glucopyranoside ligase, mycothiol biosynthesis enzyme MshC, is related to
RT class I cysteinyl-tRNA synthetases.";
RL Biochemistry 41:6885-6890(2002).
RN [5]
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND ENZYME KINETICS.
RX PubMed=17848100; DOI=10.1021/bi7011492;
RA Fan F., Luxenburger A., Painter G.F., Blanchard J.S.;
RT "Steady-state and pre-steady-state kinetic analysis of Mycobacterium
RT smegmatis cysteine ligase (MshC).";
RL Biochemistry 46:11421-11429(2007).
RN [6]
RP MUTAGENESIS OF THR-46; HIS-55; THR-83; TRP-227 AND ASP-251.
RX PubMed=19505149; DOI=10.1021/bi900457x;
RA Fan F., Blanchard J.S.;
RT "Toward the catalytic mechanism of a cysteine ligase (MshC) from
RT Mycobacterium smegmatis: an enzyme involved in the biosynthetic pathway of
RT mycothiol.";
RL Biochemistry 48:7150-7159(2009).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH ZINC AND CYSTEINYL
RP ADENYLATE ANALOG.
RX PubMed=19053270; DOI=10.1021/bi801708f;
RA Tremblay L.W., Fan F., Vetting M.W., Blanchard J.S.;
RT "The 1.6 A crystal structure of Mycobacterium smegmatis MshC: the
RT penultimate enzyme in the mycothiol biosynthetic pathway.";
RL Biochemistry 47:13326-13335(2008).
CC -!- FUNCTION: Catalyzes the ATP-dependent condensation of GlcN-Ins and L-
CC cysteine to form L-Cys-GlcN-Ins.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 2-amino-2-deoxy-alpha-D-glucopyranoside + ATP
CC + L-cysteine = 1D-myo-inositol 2-(L-cysteinylamino)-2-deoxy-alpha-D-
CC glucopyranoside + AMP + diphosphate + H(+); Xref=Rhea:RHEA:26176,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:35235, ChEBI:CHEBI:58886, ChEBI:CHEBI:58887,
CC ChEBI:CHEBI:456215; EC=6.3.1.13;
CC Evidence={ECO:0000269|PubMed:12033919};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 1 zinc ion per subunit.;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=40 uM for L-cysteine {ECO:0000269|PubMed:12033919,
CC ECO:0000269|PubMed:17848100};
CC KM=72 uM for GlcN-Ins {ECO:0000269|PubMed:12033919,
CC ECO:0000269|PubMed:17848100};
CC KM=1.84 mM for ATP {ECO:0000269|PubMed:12033919,
CC ECO:0000269|PubMed:17848100};
CC Vmax=83 nmol/min/mg enzyme {ECO:0000269|PubMed:12033919,
CC ECO:0000269|PubMed:17848100};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:17848100,
CC ECO:0000269|PubMed:19053270}.
CC -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family.
CC MshC subfamily. {ECO:0000305}.
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DR EMBL; CP000480; ABK74756.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP40549.1; -; Genomic_DNA.
DR RefSeq; WP_011729628.1; NZ_SIJM01000003.1.
DR RefSeq; YP_888468.1; NC_008596.1.
DR PDB; 3C8Z; X-ray; 1.60 A; A/B=1-412.
DR PDBsum; 3C8Z; -.
DR AlphaFoldDB; A0QZY0; -.
DR SMR; A0QZY0; -.
DR STRING; 246196.MSMEI_4091; -.
DR EnsemblBacteria; ABK74756; ABK74756; MSMEG_4189.
DR EnsemblBacteria; AFP40549; AFP40549; MSMEI_4091.
DR GeneID; 66735536; -.
DR KEGG; msg:MSMEI_4091; -.
DR KEGG; msm:MSMEG_4189; -.
DR PATRIC; fig|246196.19.peg.4110; -.
DR eggNOG; COG0215; Bacteria.
DR OMA; HAWPASE; -.
DR OrthoDB; 952207at2; -.
DR BioCyc; MetaCyc:MON-9641; -.
DR BioCyc; MetaCyc:MON-9682; -.
DR BRENDA; 6.3.1.13; 3512.
DR SABIO-RK; A0QZY0; -.
DR EvolutionaryTrace; A0QZY0; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0035446; F:cysteine-glucosaminylinositol ligase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0010125; P:mycothiol biosynthetic process; IEA:UniProtKB-UniRule.
DR CDD; cd00672; CysRS_core; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR HAMAP; MF_01697; MshC; 1.
DR InterPro; IPR024909; Cys-tRNA/MSH_ligase.
DR InterPro; IPR017812; Mycothiol_ligase_MshC.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR InterPro; IPR032678; tRNA-synt_1_cat_dom.
DR PANTHER; PTHR10890; PTHR10890; 1.
DR Pfam; PF01406; tRNA-synt_1e; 1.
DR PRINTS; PR00983; TRNASYNTHCYS.
DR TIGRFAMs; TIGR03447; mycothiol_MshC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Direct protein sequencing; Ligase;
KW Metal-binding; Nucleotide-binding; Reference proteome; Zinc.
FT CHAIN 1..412
FT /note="L-cysteine:1D-myo-inositol 2-amino-2-deoxy-alpha-D-
FT glucopyranoside ligase"
FT /id="PRO_0000399827"
FT MOTIF 45..55
FT /note="'HIGH' region"
FT MOTIF 187..192
FT /note="'ERGGDP' region"
FT MOTIF 289..293
FT /note="'KMSKS' region"
FT BINDING 43..46
FT /ligand="L-cysteinyl-5'-AMP"
FT /ligand_id="ChEBI:CHEBI:144924"
FT BINDING 43
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19053270"
FT BINDING 58
FT /ligand="L-cysteinyl-5'-AMP"
FT /ligand_id="ChEBI:CHEBI:144924"
FT BINDING 81..83
FT /ligand="L-cysteinyl-5'-AMP"
FT /ligand_id="ChEBI:CHEBI:144924"
FT BINDING 227
FT /ligand="L-cysteinyl-5'-AMP"
FT /ligand_id="ChEBI:CHEBI:144924"
FT BINDING 231
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19053270"
FT BINDING 249..251
FT /ligand="L-cysteinyl-5'-AMP"
FT /ligand_id="ChEBI:CHEBI:144924"
FT BINDING 256
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19053270"
FT BINDING 283
FT /ligand="L-cysteinyl-5'-AMP"
FT /ligand_id="ChEBI:CHEBI:144924"
FT MUTAGEN 46
FT /note="T->V: 100-fold decrease in catalytic turnover."
FT /evidence="ECO:0000269|PubMed:19505149"
FT MUTAGEN 55
FT /note="H->A: 40-fold decrease in catalytic turnover."
FT /evidence="ECO:0000269|PubMed:19505149"
FT MUTAGEN 83
FT /note="T->V: Almost no effect."
FT /evidence="ECO:0000269|PubMed:19505149"
FT MUTAGEN 227
FT /note="W->F,H: 100-fold decrease in catalytic turnover."
FT /evidence="ECO:0000269|PubMed:19505149"
FT MUTAGEN 251
FT /note="D->A: 1200-fold decfrease in catalytic turnover."
FT /evidence="ECO:0000269|PubMed:19505149"
FT MUTAGEN 251
FT /note="D->N: 400-fold decrease in catalytic turnover."
FT /evidence="ECO:0000269|PubMed:19505149"
FT STRAND 20..23
FT /evidence="ECO:0007829|PDB:3C8Z"
FT TURN 24..27
FT /evidence="ECO:0007829|PDB:3C8Z"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:3C8Z"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 53..71
FT /evidence="ECO:0007829|PDB:3C8Z"
FT STRAND 75..82
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 87..96
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 100..117
FT /evidence="ECO:0007829|PDB:3C8Z"
FT STRAND 124..128
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 133..145
FT /evidence="ECO:0007829|PDB:3C8Z"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:3C8Z"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:3C8Z"
FT TURN 168..174
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 178..187
FT /evidence="ECO:0007829|PDB:3C8Z"
FT STRAND 203..208
FT /evidence="ECO:0007829|PDB:3C8Z"
FT STRAND 222..225
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 227..238
FT /evidence="ECO:0007829|PDB:3C8Z"
FT STRAND 243..249
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:3C8Z"
FT TURN 253..255
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 256..268
FT /evidence="ECO:0007829|PDB:3C8Z"
FT STRAND 273..280
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 300..305
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 310..318
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 330..347
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 356..367
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 372..389
FT /evidence="ECO:0007829|PDB:3C8Z"
FT STRAND 392..395
FT /evidence="ECO:0007829|PDB:3C8Z"
FT HELIX 396..408
FT /evidence="ECO:0007829|PDB:3C8Z"
SQ SEQUENCE 412 AA; 45399 MW; F9283E2F60714E3F CRC64;
MQSWSAPAIP VVPGRGPALR LFDSADRQVR PVTPGPTATM YVCGITPYDA THLGHAATYL
TFDLVHRLWL DAGHTVQYVQ NVTDVDDPLF ERAERDGIDW RTLGDRETQL FREDMAALRV
LPPHDYVAAT DAIAEVVEMV EKLLASGAAY IVEDAEYPDV YFRADATAQF GYESGYDRDT
MLTLFAERGG DPDRPGKSDQ LDALLWRAER PGEPSWPSPF GRGRPGWHVE CSAIALTRIG
TGLDIQGGGS DLIFPHHEYS AAHAESVTGE RRFARHYVHT GMIGWDGHKM SKSRGNLVLV
SQLRAQGVDP SAIRLGLFSG HYREDRFWSN EVLDEANARL ARWRSATALP EAPDATDVIA
RVRQYLADDL DTPKALAALD GWCTDALSYG GHDTESPRLV ATTVDALLGV DL
