GRSA_ANEMI
ID GRSA_ANEMI Reviewed; 1098 AA.
AC P0C061; P14687;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Gramicidin S synthase 1;
DE AltName: Full=Gramicidin S synthase I;
DE Includes:
DE RecName: Full=ATP-dependent D-phenylalanine adenylase;
DE Short=D-PheA;
DE AltName: Full=D-phenylalanine activase;
DE Includes:
DE RecName: Full=Phenylalanine racemase [ATP-hydrolyzing];
DE EC=5.1.1.11;
GN Name=grsA; Synonyms=grs1;
OS Aneurinibacillus migulanus (Bacillus migulanus).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Paenibacillaceae;
OC Aneurinibacillus group; Aneurinibacillus.
OX NCBI_TaxID=47500;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 9999 / DSM 2895 / JCM 8504 / NBRC 15520 / NCIMB 7096 / NCTC
RC 7096;
RX PubMed=2477357; DOI=10.1128/jb.171.10.5422-5429.1989;
RA Kraetzschmar J., Krause M., Marahiel M.A.;
RT "Gramicidin S biosynthesis operon containing the structural genes grsA and
RT grsB has an open reading frame encoding a protein homologous to fatty acid
RT thioesterases.";
RL J. Bacteriol. 171:5422-5429(1989).
RN [2]
RP PROTEIN SEQUENCE OF 564-575, COFACTOR, AND PHOSPHOPANTETHEINYLATION AT
RP SER-573.
RC STRAIN=ATCC 9999 / DSM 2895 / JCM 8504 / NBRC 15520 / NCIMB 7096 / NCTC
RC 7096;
RX PubMed=7718566; DOI=10.1021/bi00014a017;
RA Stein T., Kluge B., Vater J., Franke P., Otto A., Wittmann-Liebold B.;
RT "Gramicidin S synthetase 1 (phenylalanine racemase), a prototype of amino
RT acid racemases containing the cofactor 4'-phosphopantetheine.";
RL Biochemistry 34:4633-4642(1995).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 17-530, AND SEQUENCE REVISION TO
RP 335.
RC STRAIN=ATCC 9999 / DSM 2895 / JCM 8504 / NBRC 15520 / NCIMB 7096 / NCTC
RC 7096;
RX PubMed=9250661; DOI=10.1093/emboj/16.14.4174;
RA Conti E., Stachelhaus T., Marahiel M.A., Brick P.;
RT "Structural basis for the activation of phenylalanine in the non-ribosomal
RT biosynthesis of gramicidin S.";
RL EMBO J. 16:4174-4183(1997).
CC -!- FUNCTION: In the first step of peptide synthesis this enzyme activates
CC phenylalanine and racemizes it to the D-isomer.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + L-phenylalanine = AMP + D-phenylalanine +
CC diphosphate + H(+); Xref=Rhea:RHEA:20201, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57981, ChEBI:CHEBI:58095, ChEBI:CHEBI:456215;
CC EC=5.1.1.11;
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000269|PubMed:7718566};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000269|PubMed:7718566};
CC -!- PATHWAY: Antibiotic biosynthesis; gramicidin S biosynthesis.
CC -!- SUBUNIT: Large multienzyme complex of GrsA and GrsB.
CC -!- DOMAIN: One-module-bearing peptide synthase with a C-terminal
CC epimerization domain. Each module incorporates one amino acid into the
CC peptide product and can be further subdivided into domains responsible
CC for substrate adenylation, thiolation, condensation (not for the
CC initiation module), and epimerization (optional), and N methylation
CC (optional).
CC -!- MISCELLANEOUS: The racemization reaction takes place in the thioester-
CC bound stage of phenylalanine that is formed via the thiol group of the
CC serine-bound phosphopantetheine.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; M29703; AAA58718.1; -; Genomic_DNA.
DR EMBL; X15577; CAA33603.1; -; Genomic_DNA.
DR PIR; JU0122; YGBSG1.
DR RefSeq; WP_043064678.1; NZ_LGUG01000004.1.
DR PDB; 1AMU; X-ray; 1.90 A; A/B=3-556.
DR PDBsum; 1AMU; -.
DR AlphaFoldDB; P0C061; -.
DR SMR; P0C061; -.
DR STRING; 47500.AF333_17650; -.
DR OrthoDB; 572620at2; -.
DR BioCyc; MetaCyc:MON-14128; -.
DR UniPathway; UPA00102; -.
DR EvolutionaryTrace; P0C061; -.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0047462; F:phenylalanine racemase (ATP-hydrolyzing) activity; IEA:UniProtKB-EC.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:1901576; P:organic substance biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR010060; NRPS_synth.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR TIGRFAMs; TIGR01720; NRPS-para261; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; ATP-binding;
KW Direct protein sequencing; Isomerase; Ligase; Multifunctional enzyme;
KW Nucleotide-binding; Phosphopantetheine; Phosphoprotein.
FT CHAIN 1..1098
FT /note="Gramicidin S synthase 1"
FT /id="PRO_0000193085"
FT DOMAIN 538..612
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 573
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000269|PubMed:7718566"
FT CONFLICT 335
FT /note="W -> C (in Ref. 1; AAA58718)"
FT /evidence="ECO:0000305"
FT HELIX 20..27
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 41..51
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 55..60
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 63..66
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 67..83
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 100..111
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 125..135
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 147..150
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:1AMU"
FT TURN 166..169
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 183..190
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 198..204
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 205..216
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 225..228
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 236..245
FT /evidence="ECO:0007829|PDB:1AMU"
FT TURN 246..248
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 250..253
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 262..271
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 276..279
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 281..284
FT /evidence="ECO:0007829|PDB:1AMU"
FT TURN 289..291
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 296..303
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 307..313
FT /evidence="ECO:0007829|PDB:1AMU"
FT TURN 314..316
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 317..323
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 326..328
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 332..336
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 349..351
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 355..360
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 372..379
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 390..396
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 397..399
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 406..417
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 423..428
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 429..431
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 432..435
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 438..441
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 442..449
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 455..464
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 470..480
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 484..494
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 497..499
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 502..506
FT /evidence="ECO:0007829|PDB:1AMU"
FT STRAND 516..518
FT /evidence="ECO:0007829|PDB:1AMU"
FT HELIX 520..522
FT /evidence="ECO:0007829|PDB:1AMU"
SQ SEQUENCE 1098 AA; 126632 MW; A4FD8282FE4AF2F4 CRC64;
MLNSSKSILI HAQNKNGTHE EEQYLFAVNN TKAEYPRDKT IHQLFEEQVS KRPNNVAIVC
ENEQLTYHEL NVKANQLARI FIEKGIGKDT LVGIMMEKSI DLFIGILAVL KAGGAYVPID
IEYPKERIQY ILDDSQARML LTQKHLVHLI HNIQFNGQVE IFEEDTIKIR EGTNLHVPSK
STDLAYVIYT SGTTGNPKGT MLEHKGISNL KVFFENSLNV TEKDRIGQFA SISFDASVWE
MFMALLTGAS LYIILKDTIN DFVKFEQYIN QKEITVITLP PTYVVHLDPE RILSIQTLIT
AGSATSPSLV NKWKEKVTYI NAYGPTETTI CATTWVATKE TIGHSVPIGA PIQNTQIYIV
DENLQLKSVG EAGELCIGGE GLARGYWKRP ELTSQKFVDN PFVPGEKLYK TGDQARWLSD
GNIEYLGRID NQVKIRGHRV ELEEVESILL KHMYISETAV SVHKDHQEQP YLCAYFVSEK
HIPLEQLRQF SSEELPTYMI PSYFIQLDKM PLTSNGKIDR KQLPEPDLTF GMRVDYEAPR
NEIEETLVTI WQDVLGIEKI GIKDNFYALG GDSIKAIQVA ARLHSYQLKL ETKDLLKYPT
IDQLVHYIKD SKRRSEQGIV EGEIGLTPIQ HWFFEQQFTN MHHWNQSYML YRPNGFDKEI
LLRVFNKIVE HHDALRMIYK HHNGKIVQIN RGLEGTLFDF YTFDLTANDN EQQVICEESA
RLQNSINLEV GPLVKIALFH TQNGDHLFMA IHHLVVDGIS WRILFEDLAT AYEQAMHQQT
IALPEKTDSF KDWSIELEKY ANSELFLEEA EYWHHLNYYT ENVQIKKDYV TMNNKQKNIR
YVGMELTIEE TEKLLKNVNK AYRTEINDIL LTALGFALKE WADIDKIVIN LEGHGREEIL
EQMNIARTVG WFTSQYPVVL DMQKSDDLSY QIKLMKENLR RIPNKGIGYE IFKYLTTEYL
RPVLPFTLKP EINFNYLGQF DTDVKTELFT RSPYSMGNSL GPDGKNNLSP EGESYFVLNI
NGFIEEGKLH ITFSYNEQQY KEDTIQQLSR SYKQHLLAII EHCVQKEDTE LTPSDFSFKE
LELEEMDDIF DLLADSLT
