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| Enzyme Name | | UniProtKB | KEGG |
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| P0C061 | P0C062 |
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| Protein name | Gramicidin S synthetase 1 | Gramicidin S synthetase 1 | phenylalanine racemase (ATP-hydrolysing)phenylalanine racemasephenylalanine racemase (adenosine triphosphate-hydrolysing)gramicidin S synthetase I |
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| Synonyms | Gramicidin S synthetase I | Gramicidin S synthetase I |
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| Includes | ATP-dependent D-phenylalanine adenylase(D-PheA)D-phenylalanine activasePhenylalanine racemase {ATP-hydrolyzing} EC 5.1.1.11 | ATP-dependent D-phenylalanine adenylase(D-PheA)D-phenylalanine activasePhenylalanine racemase {ATP-hydrolyzing} EC 5.1.1.11 |
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| Pfam | PF00501 (AMP-binding)
PF00668 (Condensation)
PF00550 (PP-binding)
[Graphical view]
| PF00501 (AMP-binding)
PF00668 (Condensation)
PF00550 (PP-binding)
[Graphical view]
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| KEGG pathways | | MAP code | Pathways |
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| MAP00360 | Phenylalanine metabolism |
| UniProtKB:Accession Number | P0C061 | P0C062 |
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| Entry name | GRSA_ANEMI | GRSA_BREBE |
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| Activity | ATP + L-phenylalanine + H(2)O = AMP + diphosphate + D-phenylalanine. | ATP + L-phenylalanine + H(2)O = AMP + diphosphate + D-phenylalanine. |
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| Subunit | Large multienzyme complex of grsA and grsB. | Large multienzyme complex of grsA and grsB (By similarity). |
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| Subcellular location |
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| Cofactor | Binds 1 phosphopantetheine covalently. | Binds 1 phosphopantetheine covalently (By similarity). |
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| References for Catalytic Mechanism | | References | Sections | No. of steps in catalysis |
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| [5] | Fig.1, Fig.3 |
| | [7] | Fig.1 |
| | [8] | Fig.1 |
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| references | | [1] |
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| PubMed ID | 7309699 |
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| Journal | J Biochem (Tokyo) |
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| Year | 1981 |
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| Volume | 90 |
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| Pages | 765-71 |
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| Authors | Kanda M, Hori K, Kurotsu T, Miura S, Yamada Y, Saito Y |
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| Title | Sulfhydryl groups related to the catalytic activity of gramicidin S synthetase 1 of Bacillus brevis. |
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| [2] |
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| PubMed ID | 6188751 |
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| Journal | J Biochem (Tokyo) |
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| Year | 1983 |
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| Volume | 93 |
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| Pages | 177-88 |
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| Authors | Hori K, Kanda M, Miura S, Yamada Y, Saito Y |
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| Title | Transfer of D-phenylalanine from gramicidin S synthetase 1 to gramicidin S synthetase 2 in gramicidin S synthesis. |
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| [3] |
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| Comments | X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 17-530, AND REVISION TO 335. |
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| Medline ID | 97392447 |
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| PubMed ID | 9250661 |
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| Journal | EMBO J |
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| Year | 1997 |
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| Volume | 16 |
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| Pages | 4174-83 |
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| Authors | Conti E, Stachelhaus T, Marahiel MA, Brick P |
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| Title | Structural basis for the activation of phenylalanine in the non-ribosomal biosynthesis of gramicidin S. |
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| Related PDB | 1amu |
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| Related UniProtKB | P0C061 |
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| [4] |
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| PubMed ID | 9246644 |
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| Journal | J Protein Chem |
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| Year | 1997 |
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| Volume | 16 |
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| Pages | 557-64 |
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| Authors | Vater J, Stein T, Vollenbroich D, Kruft V, Wittmann-Liebold B, Franke P, Liu L, Zuber P |
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| Title | The modular organization of multifunctional peptide synthetases. |
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| [5] |
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| PubMed ID | 10801328 |
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| Journal | Biochemistry |
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| Year | 2000 |
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| Volume | 39 |
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| Pages | 5775-87 |
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| Authors | Stachelhaus T, Walsh CT |
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| Title | Mutational analysis of the epimerization domain in the initiation module PheATE of gramicidin S synthetase. |
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| [6] |
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| PubMed ID | 10712928 |
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| Journal | Chem Biol |
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| Year | 2000 |
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| Volume | 7 |
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| Pages | 211-24 |
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| Authors | Challis GL, Ravel J, Townsend CA |
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| Title | Predictive, structure-based model of amino acid recognition by nonribosomal peptide synthetase adenylation domains. |
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| [7] |
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| PubMed ID | 11330995 |
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| Journal | Biochemistry |
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| Year | 2001 |
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| Volume | 40 |
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| Pages | 5329-37 |
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| Authors | Luo L, Walsh CT |
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| Title | Kinetic analysis of three activated phenylalanyl intermediates generated by the initiation module PheATE of gramicidin S synthetase. |
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| [8] |
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| PubMed ID | 11697963 |
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| Journal | J Am Chem Soc |
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| Year | 2001 |
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| Volume | 123 |
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| Pages | 11208-18 |
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| Authors | Luo L, Burkart MD, Stachelhaus T, Walsh CT |
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| Title | Substrate recognition and selection by the initiation module PheATE of gramicidin S synthetase. |
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| comments | This enzyme is composed of three functional domains, the N-terminal adenylase domain, acyl carrier domain, and the C-terminal epimerase domain (see [5]). The second acyl carrier domain binds phosphopantetheine covalently.
The structure of the N-terminal domain, which itself has four units, has only been determined so far.
According to the literature [5], [7] & [8], this enzyme catalyzes the following reactions successively.
(A) Transfer of adenylate from ATP to the carboxylate oxygen of L-phenylalanine. (This reaction occurs at the N-terminal domain.)
ATP + L-phenylalanine = L-phenylalanyl-adenosine-5'-phsphate diester.
(B) Transfer of acyl group from the adenylated phenylalanine to thiol group of the phosphopantetheine cofactor on the acyl carrier domain, releasing AMP as leaving group. (This reaction occurs at the acyl carrier domain.)
L-Phenylalanyl-adenosine-5'-phsphate diester + phosphopantetheine-acyl enzyme = L-phenylalanyl-S-4'-phosphopantetheine-acyl enzyme + AMP.
(C) Isomerization (shift of double-bond position)
(C') Isomerization (shift of double-bond position) (These reactions occur on the C-terminal epimerase domain.)
L-phenylalanyl-S-4'-phosphopantetheine-acyl enzyme = D-phenylalanyl-S-4'-phosphopantetheine-acyl enzyme.
(D) Removal of D-phenylalanine from the cofactor. This reaction probably carried out by gramicidin S synthetase II (swiss-prot;P14688), which synthesises gramicidin S.
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| created | updated |
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| 2005-06-15 | 2009-02-26 |
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