ID   GCVHL_STRPG             Reviewed;         110 AA.
AC   P0DN69;
DT   20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT   20-JAN-2016, sequence version 1.
DT   25-MAY-2022, entry version 22.
DE   RecName: Full=Glycine cleavage system H-like protein {ECO:0000303|PubMed:26166706};
DE            Short=GcvH-L {ECO:0000303|PubMed:26166706};
GN   OrderedLocusNames=SpyM50867 {ECO:0000312|EMBL:CAM30195.1};
OS   Streptococcus pyogenes serotype M5 (strain Manfredo).
OC   Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC   Streptococcus.
OX   NCBI_TaxID=160491;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Manfredo;
RX   PubMed=17012393; DOI=10.1128/jb.01227-06;
RA   Holden M.T.G., Scott A., Cherevach I., Chillingworth T., Churcher C.,
RA   Cronin A., Dowd L., Feltwell T., Hamlin N., Holroyd S., Jagels K.,
RA   Moule S., Mungall K., Quail M.A., Price C., Rabbinowitsch E., Sharp S.,
RA   Skelton J., Whitehead S., Barrell B.G., Kehoe M., Parkhill J.;
RT   "Complete genome of acute rheumatic fever-associated serotype M5
RT   Streptococcus pyogenes strain Manfredo.";
RL   J. Bacteriol. 189:1473-1477(2007).
RN   [2]
RP   X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS), FUNCTION, LIPOYLATION AT LYS-56,
RP   ADP-RIBOSYLATION AT ASP-27, MUTAGENESIS OF GLU-11; GLU-24; ASP-27; ASP-28;
RP   ASP-46; ASP-47; GLU-53 AND LYS-56, AND INTERACTION WITH SPYM50868 AND
RP   SPYM50865.
RC   STRAIN=Manfredo;
RX   PubMed=26166706; DOI=10.1016/j.molcel.2015.06.013;
RA   Rack J.G., Morra R., Barkauskaite E., Kraehenbuehl R., Ariza A., Qu Y.,
RA   Ortmayer M., Leidecker O., Cameron D.R., Matic I., Peleg A.Y., Leys D.,
RA   Traven A., Ahel I.;
RT   "Identification of a class of protein ADP-ribosylating sirtuins in
RT   microbial pathogens.";
RL   Mol. Cell 59:309-320(2015).
CC   -!- FUNCTION: May act as a carrier protein for the ROS scavenging lipoyl
CC       moiety and/or as a substrate for oxidoreductases such as SpyM50865 and
CC       SpyM50866. {ECO:0000305|PubMed:26166706}.
CC   -!- SUBUNIT: Lipoylated GcvH-L directly interacts with SpyM50868, which
CC       reverses the SirTM-mediated mono-ADP-ribosylation of GcvH-L, and with
CC       the oxidoreductase SpyM50865. {ECO:0000269|PubMed:26166706}.
CC   -!- PTM: Is lipoylated on K-56 by LplA2 (SpyM50870) and then mono-ADP-
CC       ribosylated on D-27 by SirTM (SpyM50869). The mono-ADP-ribosylation
CC       state of GcvH-L might regulate the availability of the lipoyl moiety
CC       for redox reactions; ADP-ribosylation would inhibit the interaction of
CC       the oxidoreductase with GcvH-L when it is not required, thus ADP-
CC       ribosylation of GcvH-L might be acting to keep the response 'off' under
CC       non-stress conditions. {ECO:0000269|PubMed:26166706}.
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DR   EMBL; AM295007; CAM30195.1; -; Genomic_DNA.
DR   RefSeq; WP_002984553.1; NC_009332.1.
DR   PDB; 5A35; X-ray; 1.50 A; A=1-110.
DR   PDBsum; 5A35; -.
DR   AlphaFoldDB; P0DN69; -.
DR   SMR; P0DN69; -.
DR   GeneID; 57852687; -.
DR   KEGG; spf:SpyM50867; -.
DR   HOGENOM; CLU_097408_3_0_9; -.
DR   OMA; ENWVMIL; -.
DR   CDD; cd06848; GCS_H; 1.
DR   InterPro; IPR003016; 2-oxoA_DH_lipoyl-BS.
DR   InterPro; IPR033753; GCV_H/Fam206.
DR   InterPro; IPR011053; Single_hybrid_motif.
DR   Pfam; PF01597; GCV_H; 1.
DR   SUPFAM; SSF51230; SSF51230; 1.
DR   PROSITE; PS00189; LIPOYL; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ADP-ribosylation; Lipoyl.
FT   CHAIN           1..110
FT                   /note="Glycine cleavage system H-like protein"
FT                   /id="PRO_0000435341"
FT   DOMAIN          16..97
FT                   /note="Lipoyl-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT   MOD_RES         27
FT                   /note="ADP-ribosyl aspartic acid"
FT                   /evidence="ECO:0000269|PubMed:26166706"
FT   MOD_RES         56
FT                   /note="N6-lipoyllysine"
FT                   /evidence="ECO:0000269|PubMed:26166706"
FT   MUTAGEN         11
FT                   /note="E->A: No effect on ADP-ribosylation."
FT                   /evidence="ECO:0000269|PubMed:26166706"
FT   MUTAGEN         24
FT                   /note="E->A: Large decrease in ADP-ribosylation."
FT                   /evidence="ECO:0000269|PubMed:26166706"
FT   MUTAGEN         27
FT                   /note="D->A: Total loss of ADP-ribosylation."
FT                   /evidence="ECO:0000269|PubMed:26166706"
FT   MUTAGEN         28
FT                   /note="D->A: No effect on ADP-ribosylation."
FT                   /evidence="ECO:0000269|PubMed:26166706"
FT   MUTAGEN         46
FT                   /note="D->A: No effect on ADP-ribosylation."
FT                   /evidence="ECO:0000269|PubMed:26166706"
FT   MUTAGEN         47
FT                   /note="D->A: No effect on ADP-ribosylation."
FT                   /evidence="ECO:0000269|PubMed:26166706"
FT   MUTAGEN         53
FT                   /note="E->Q: Decrease in lipoylation."
FT                   /evidence="ECO:0000269|PubMed:26166706"
FT   MUTAGEN         56
FT                   /note="K->R: Loss of lipoylation."
FT                   /evidence="ECO:0000269|PubMed:26166706"
SQ   SEQUENCE   110 AA;  12088 MW;  37387EB33DF59A46 CRC64;
     MKKIANYLLI EKTDDRYTIS MTPELQDDIG TIGYAEFTDN DHLAVDDIIL NLEASKTVMS
     VLSPLAGAVV ERNEAATLTP TLLNSEKAEE NWIVVLTDVD QAAFDALEDA