VGB_STAAU
ID VGB_STAAU Reviewed; 299 AA.
AC P17978; Q53744;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Virginiamycin B lyase;
DE EC=4.2.99.-;
DE AltName: Full=Streptogramin B lyase;
GN Name=vgb; Synonyms=vgh;
OS Staphylococcus aureus.
OG Plasmid pIP630, and Plasmid pIP524.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1280;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC PLASMID=pIP630;
RX PubMed=3149758; DOI=10.1016/0147-619x(88)90034-0;
RA Allignet J., Loncle V., Mazodier P., El Solh N.;
RT "Nucleotide sequence of a staphylococcal plasmid gene, vgb, encoding a
RT hydrolase inactivating the B components of virginiamycin-like
RT antibiotics.";
RL Plasmid 20:271-275(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=BM3093; PLASMID=pIP630;
RX PubMed=10489330; DOI=10.1006/plas.1999.1412;
RA Allignet J., El Solh N.;
RT "Comparative analysis of staphylococcal plasmids carrying three
RT streptogramin-resistance genes: vat-vgb-vga.";
RL Plasmid 42:134-138(1999).
RN [3]
RP FUNCTION AS A LYASE, REACTION MECHANISM, SUBSTRATE SPECIFICITY, SUBUNIT,
RP COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=BM3002; PLASMID=pIP524;
RX PubMed=11467949; DOI=10.1021/bi0106787;
RA Mukhtar T.A., Koteva K.P., Hughes D.W., Wright G.D.;
RT "Vgb from Staphylococcus aureus inactivates streptogramin B antibiotics by
RT an elimination mechanism not hydrolysis.";
RL Biochemistry 40:8877-8886(2001).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF WILD-TYPE AND MUTANT ALA-270 IN
RP COMPLEX WITH QUINUPRISTIN AND MAGNESIUM, CATALYTIC MECHANISM,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF TYR-18; HIS-228; GLU-268;
RP HIS-270 AND GLU-284.
RC STRAIN=BM3002; PLASMID=pIP524;
RX PubMed=17563376; DOI=10.1073/pnas.0701809104;
RA Korczynska M., Mukhtar T.A., Wright G.D., Berghuis A.M.;
RT "Structural basis for streptogramin B resistance in Staphylococcus aureus
RT by virginiamycin B lyase.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:10388-10393(2007).
CC -!- FUNCTION: Inactivates the type B streptogramin antibiotics by
CC linearizing the lactone ring at the ester linkage, generating a free
CC phenylglycine carboxylate and converting the threonyl moiety into 2-
CC amino-butenoic acid. {ECO:0000269|PubMed:11467949}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11467949};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8 uM for quinupristin {ECO:0000269|PubMed:11467949,
CC ECO:0000269|PubMed:17563376};
CC KM=19 uM for pristinamycin IA {ECO:0000269|PubMed:11467949,
CC ECO:0000269|PubMed:17563376};
CC KM=0.19 mM for magnesium {ECO:0000269|PubMed:11467949,
CC ECO:0000269|PubMed:17563376};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11467949,
CC ECO:0000269|PubMed:17563376}.
CC -!- MISCELLANEOUS: Has unequivocally been shown (PubMed:11467949) to cleave
CC the ester bond of streptogramin B antibiotics by an elimination
CC reaction and not by hydrolysis, therefore is a lyase and not a
CC hydrolase. The olefinic dehydrobutyrine thus generated in the N-
CC terminal position has a Z stereochemistry.
CC {ECO:0000305|PubMed:11467949}.
CC -!- SIMILARITY: Belongs to the Vgb family. {ECO:0000305}.
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DR EMBL; M36022; AAA98259.1; -; Genomic_DNA.
DR EMBL; M20129; AAA98349.1; -; Genomic_DNA.
DR EMBL; AF117258; AAF24088.1; -; Genomic_DNA.
DR PIR; S27668; PN0638.
DR RefSeq; WP_032489636.1; NG_048563.1.
DR PDB; 2Z2N; X-ray; 1.65 A; A=1-299.
DR PDB; 2Z2O; X-ray; 1.90 A; A/B/C/D=1-299.
DR PDB; 2Z2P; X-ray; 2.80 A; A/B=1-299.
DR PDBsum; 2Z2N; -.
DR PDBsum; 2Z2O; -.
DR PDBsum; 2Z2P; -.
DR AlphaFoldDB; P17978; -.
DR SMR; P17978; -.
DR KEGG; ag:AAA98349; -.
DR SABIO-RK; P17978; -.
DR EvolutionaryTrace; P17978; -.
DR GO; GO:0016835; F:carbon-oxygen lyase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0017001; P:antibiotic catabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 2.130.10.10; -; 1.
DR HAMAP; MF_01282; VirginiamycinB_lyase; 1.
DR InterPro; IPR011217; Streptogrm_lyase.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR PIRSF; PIRSF026412; Streptogrm_lyase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; Lyase; Magnesium; Metal-binding;
KW Plasmid.
FT CHAIN 1..299
FT /note="Virginiamycin B lyase"
FT /id="PRO_0000068590"
FT ACT_SITE 270
FT /note="Proton acceptor"
FT BINDING 228
FT /ligand="substrate"
FT BINDING 268
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:17563376"
FT BINDING 284
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:17563376"
FT MUTAGEN 18
FT /note="Y->F: 600-fold decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:17563376"
FT MUTAGEN 228
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17563376"
FT MUTAGEN 268
FT /note="E->Q: 56-fold decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:17563376"
FT MUTAGEN 270
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17563376"
FT MUTAGEN 284
FT /note="E->Q: 137-fold decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:17563376"
FT CONFLICT 267
FT /note="G -> A (in Ref. 1; AAA98349 and 2; AAF24088)"
FT /evidence="ECO:0000305"
FT STRAND 3..9
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 12..14
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 17..22
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:2Z2P"
FT STRAND 28..32
FT /evidence="ECO:0007829|PDB:2Z2N"
FT TURN 33..36
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 37..41
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 47..51
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:2Z2P"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 70..74
FT /evidence="ECO:0007829|PDB:2Z2N"
FT TURN 75..78
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 89..93
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 101..106
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 112..116
FT /evidence="ECO:0007829|PDB:2Z2N"
FT TURN 117..120
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 131..135
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 154..158
FT /evidence="ECO:0007829|PDB:2Z2N"
FT TURN 159..162
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 173..177
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 185..190
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 194..200
FT /evidence="ECO:0007829|PDB:2Z2N"
FT TURN 201..204
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 205..209
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 215..219
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 227..232
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 238..242
FT /evidence="ECO:0007829|PDB:2Z2N"
FT TURN 243..246
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 247..252
FT /evidence="ECO:0007829|PDB:2Z2N"
FT TURN 253..255
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 256..261
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 263..266
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 269..274
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 279..283
FT /evidence="ECO:0007829|PDB:2Z2N"
FT TURN 284..286
FT /evidence="ECO:0007829|PDB:2Z2N"
FT STRAND 287..293
FT /evidence="ECO:0007829|PDB:2Z2N"
SQ SEQUENCE 299 AA; 33058 MW; D2D35588C38FC0E3 CRC64;
MEFKLQELNL TNQDTGPYGI TVSDKGKVWI TQHKANMISC INLDGKITEY PLPTPDAKVM
CLTISSDGEV WFTENAANKI GRITKKGIIK EYTLPNPDSA PYGITEGPNG DIWFTEMNGN
RIGRITDDGK IREYELPNKG SYPSFITLGS DNALWFTENQ NNAIGRITES GDITEFKIPT
PASGPVGITK GNDDALWFVE IIGNKIGRIT PLGEITEFKI PTPNARPHAI TAGAGIDLWF
TEWGANKIGR LTSNNIIEEY PIQIKSGEPH GICFDGETIW FAMECDKIGK LTLIKDNME
