P0C061 (GRSA_ANEMI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gramicidin S synthase 1

Alternative name(s):
Gramicidin S synthase I

Including the following 2 domains:

1. ATP-dependent D-phenylalanine adenylase
   Short name=D-PheA
   Alternative name(s):
   D-phenylalanine activase
2. Phenylalanine racemase [ATP-hydrolyzing]
   EC=5.1.1.11

Gene names

Name:	grsA
Synonyms:	grs1

Organism

Aneurinibacillus migulanus (Bacillus migulanus)

Taxonomic identifier

47500 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Firmicutes › Bacilli › Bacillales › Paenibacillaceae › Aneurinibacillus group › Aneurinibacillus

Protein attributes

Sequence length	1098 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	In the first step of peptide synthesis this enzyme activates phenylalanine and racemizes it to the D-isomer.
Catalytic activity	ATP + L-phenylalanine + H2O = AMP + diphosphate + D-phenylalanine.
Cofactor	Binds 1 phosphopantetheine covalently. Ref.2
Pathway	Antibiotic biosynthesis; gramicidin S biosynthesis.
Subunit structure	Large multienzyme complex of GrsA and GrsB.
Domain	One-module-bearing peptide synthase with a C-terminal epimerization domain. Each module incorporates one amino acid into the peptide product and can be further subdivided into domains responsible for substrate adenylation, thiolation, condensation (not for the initiation module), and epimerization (optional), and N methylation (optional).
Miscellaneous	The racemization reaction takes place in the thioester-bound stage of phenylalanine that is formed via the thiol group of the serine-bound phosphopantetheine.
Sequence similarities	Belongs to the ATP-dependent AMP-binding enzyme family. Contains 1 acyl carrier domain.

Ontologies

Keywords
Biological process	Antibiotic biosynthesis
Ligand	ATP-binding Nucleotide-binding Phosphopantetheine
Molecular function	Isomerase Ligase
Technical term	3D-structure Direct protein sequencing Multifunctional enzyme
Gene Ontology (GO)
Biological_process	antibiotic biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ligase activity Inferred from electronic annotation. Source: UniProtKB-KW phenylalanine racemase (ATP-hydrolyzing) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1098

1098

Gramicidin S synthase 1

PRO_0000193085

Regions

Domain

543 – 609

67

Acyl carrier

Amino acid modifications

Modified residue

573

1

O-(pantetheine 4'-phosphoryl)serine

Experimental info

Sequence conflict

335

1

W → C in AAA58718. Ref.1

Secondary structure

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1098

Helix Strand Turn

Details...

Helix

20 – 27

8

Helix

41 – 51

11

Beta strand

55 – 60

6

Beta strand

63 – 66

4

Helix

67 – 83

17

Beta strand

91 – 95

5

Helix

100 – 111

12

Beta strand

115 – 118

4

Helix

125 – 135

11

Beta strand

138 – 142

5

Helix

144 – 146

3

Helix

147 – 150

4

Beta strand

157 – 161

5

Turn

166 – 169

4

Beta strand

183 – 190

8

Beta strand

198 – 204

7

Helix

205 – 216

12

Beta strand

225 – 228

4

Helix

236 – 245

10

Turn

246 – 248

3

Beta strand

250 – 253

4

Helix

256 – 259

4

Helix

262 – 271

10

Beta strand

276 – 279

4

Helix

281 – 284

4

Turn

289 – 291

3

Beta strand

296 – 303

8

Helix

307 – 313

7

Turn

314 – 316

3

Beta strand

317 – 323

7

Helix

326 – 328

3

Beta strand

332 – 336

5

Beta strand

349 – 351

3

Beta strand

355 – 360

6

Beta strand

372 – 379

8

Helix

390 – 396

7

Beta strand

397 – 399

3

Beta strand

401 – 403

3

Beta strand

406 – 417

12

Beta strand

423 – 428

6

Helix

429 – 431

3

Beta strand

432 – 435

4

Beta strand

438 – 441

4

Helix

442 – 449

8

Beta strand

455 – 464

10

Beta strand

470 – 480

11

Helix

484 – 494

11

Helix

497 – 499

3

Beta strand

502 – 506

5

Beta strand

516 – 518

3

Helix

520 – 522

3

Sequences

	Sequence		Length	Mass (Da)
	P0C061 [UniParc]. Last modified July 5, 2005. Version 1. Checksum: A4FD8282FE4AF2F4	FASTA	1,098	126,632
	10 20 30 40 50 60 MLNSSKSILI HAQNKNGTHE EEQYLFAVNN TKAEYPRDKT IHQLFEEQVS KRPNNVAIVC 70 80 90 100 110 120 ENEQLTYHEL NVKANQLARI FIEKGIGKDT LVGIMMEKSI DLFIGILAVL KAGGAYVPID 130 140 150 160 170 180 IEYPKERIQY ILDDSQARML LTQKHLVHLI HNIQFNGQVE IFEEDTIKIR EGTNLHVPSK 190 200 210 220 230 240 STDLAYVIYT SGTTGNPKGT MLEHKGISNL KVFFENSLNV TEKDRIGQFA SISFDASVWE 250 260 270 280 290 300 MFMALLTGAS LYIILKDTIN DFVKFEQYIN QKEITVITLP PTYVVHLDPE RILSIQTLIT 310 320 330 340 350 360 AGSATSPSLV NKWKEKVTYI NAYGPTETTI CATTWVATKE TIGHSVPIGA PIQNTQIYIV 370 380 390 400 410 420 DENLQLKSVG EAGELCIGGE GLARGYWKRP ELTSQKFVDN PFVPGEKLYK TGDQARWLSD 430 440 450 460 470 480 GNIEYLGRID NQVKIRGHRV ELEEVESILL KHMYISETAV SVHKDHQEQP YLCAYFVSEK 490 500 510 520 530 540 HIPLEQLRQF SSEELPTYMI PSYFIQLDKM PLTSNGKIDR KQLPEPDLTF GMRVDYEAPR 550 560 570 580 590 600 NEIEETLVTI WQDVLGIEKI GIKDNFYALG GDSIKAIQVA ARLHSYQLKL ETKDLLKYPT 610 620 630 640 650 660 IDQLVHYIKD SKRRSEQGIV EGEIGLTPIQ HWFFEQQFTN MHHWNQSYML YRPNGFDKEI 670 680 690 700 710 720 LLRVFNKIVE HHDALRMIYK HHNGKIVQIN RGLEGTLFDF YTFDLTANDN EQQVICEESA 730 740 750 760 770 780 RLQNSINLEV GPLVKIALFH TQNGDHLFMA IHHLVVDGIS WRILFEDLAT AYEQAMHQQT 790 800 810 820 830 840 IALPEKTDSF KDWSIELEKY ANSELFLEEA EYWHHLNYYT ENVQIKKDYV TMNNKQKNIR 850 860 870 880 890 900 YVGMELTIEE TEKLLKNVNK AYRTEINDIL LTALGFALKE WADIDKIVIN LEGHGREEIL 910 920 930 940 950 960 EQMNIARTVG WFTSQYPVVL DMQKSDDLSY QIKLMKENLR RIPNKGIGYE IFKYLTTEYL 970 980 990 1000 1010 1020 RPVLPFTLKP EINFNYLGQF DTDVKTELFT RSPYSMGNSL GPDGKNNLSP EGESYFVLNI 1030 1040 1050 1060 1070 1080 NGFIEEGKLH ITFSYNEQQY KEDTIQQLSR SYKQHLLAII EHCVQKEDTE LTPSDFSFKE 1090 LELEEMDDIF DLLADSLT

References

[1]	"Gramicidin S biosynthesis operon containing the structural genes grsA and grsB has an open reading frame encoding a protein homologous to fatty acid thioesterases." Kraetzschmar J., Krause M., Marahiel M.A. J. Bacteriol. 171:5422-5429(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 9999 / DSM 2895 / JCM 8504 / NBRC 15520 / NCTC 7096.
[2]	"Gramicidin S synthetase 1 (phenylalanine racemase), a prototype of amino acid racemases containing the cofactor 4'-phosphopantetheine." Stein T., Kluge B., Vater J., Franke P., Otto A., Wittmann-Liebold B. Biochemistry 34:4633-4642(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 564-575, COFACTOR. Strain: ATCC 9999 / DSM 2895 / JCM 8504 / NBRC 15520 / NCTC 7096.
[3]	"Structural basis for the activation of phenylalanine in the non-ribosomal biosynthesis of gramicidin S." Conti E., Stachelhaus T., Marahiel M.A., Brick P. EMBO J. 16:4174-4183(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 17-530, SEQUENCE REVISION TO 335. Strain: ATCC 9999 / DSM 2895 / JCM 8504 / NBRC 15520 / NCTC 7096.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M29703 Genomic DNA. Translation: AAA58718.1.
X15577 Genomic DNA. Translation: CAA33603.1.

PIR

YGBSG1. JU0122.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AMU	X-ray	1.90	A/B	3-556	[»]

ProteinModelPortal

P0C061.

SMR

P0C061. Positions 17-530.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-14128.

UniPathway

UPA00102.

Family and domain databases

Gene3D

1.10.1200.10. 1 hit.

InterPro

IPR010071. AA_adenyl_domain.
IPR009081. Acyl_carrier_prot-like.
IPR020845. AMP-binding_CS.
IPR000873. AMP-dep_Synth/Lig.
IPR001242. Condensatn.
IPR010060. NRPS_synth.
IPR006162. PPantetheine_attach_site.
[Graphical view]

Pfam

PF00501. AMP-binding. 1 hit.
PF00668. Condensation. 1 hit.
PF00550. PP-binding. 1 hit.
[Graphical view]

SUPFAM

SSF47336. ACP_like. 1 hit.

TIGRFAMs

TIGR01733. AA-adenyl-dom. 1 hit.
TIGR01720. NRPS-para261. 1 hit.

PROSITE

PS50075. ACP_DOMAIN. 1 hit.
PS00455. AMP_BINDING. 1 hit.
PS00012. PHOSPHOPANTETHEINE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P0C061.

Entry information

Entry name

GRSA_ANEMI

Accession

Primary (citable) accession number: P0C061
Secondary accession number(s): P14687

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	July 5, 2005
Last modified:	April 3, 2013
This is version 47 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program