DB code: S00847

RLCP classification 5.12.1497400.1 : Elimination
8.121.166300.8 : Isomerization
CATH domain 3.20.20.70 : TIM Barrel Catalytic domain
E.C. 5.3.1.24
CSA 1nsj
M-CSA 1nsj
MACiE

CATH domain Related DB codes (homologues)
3.20.20.70 : TIM Barrel S00215 S00217 S00218 S00219 S00532 S00198 S00220 S00745 S00537 S00538 S00539 S00826 S00841 S00235 S00239 S00240 S00243 S00244 S00199 S00200 S00201 S00221 S00222 S00224 S00225 S00226 D00014 D00029 M00141 T00015 T00239 D00664 D00665 D00804 D00863 T00089

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq
P83825 N-(5''-phosphoribosyl)anthranilate isomerase
EC 5.3.1.24
PF00697 (PRAI)
[Graphical View]
Q56320 N-(5''-phosphoribosyl)anthranilate isomerase
PRAI
EC 5.3.1.24
PF00697 (PRAI)
[Graphical View]
NP_227954.1 (Protein)
NC_000853.1 (DNA/RNA sequence)

KEGG enzyme name
Phosphoribosylanthranilate isomerase
PRA isomerase
PRAI
IGPS:PRAI (indole-3-glycerol-phosphate synthetase/N-5'-phosphoribosylanthranilate isomerase complex)
N-(5-phospho-beta-D-ribosyl)anthranilate ketol-isomerase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P83825 P83825_THETH N-(5-phospho-beta-D-ribosyl)anthranilate = 1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate. Homodimer.
Q56320 TRPF_THEMA N-(5-phospho-beta-D-ribosyl)anthranilate = 1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate. Homodimer.

KEGG Pathways
Map code Pathways E.C.
MAP00400 Phenylalanine, tyrosine and tryptophan biosynthesis

Compound table
Substrates Products Intermediates
KEGG-id C04302 C01302 I00057 I00058
E.C.
Compound N-(5-phospho-beta-D-ribosyl)anthranilate 1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate 1-[(2-carboxyphenyl)imino]-1-deoxyribulose 5-phosphate 1-[(2-carboxyphenyl)amino]-1-deoxyribulose 5-phosphate
Type amine group,aromatic ring (only carbon atom),carbohydrate,carboxyl group,phosphate group/phosphate ion amine group,aromatic ring (only carbon atom),carbohydrate,carboxyl group,phosphate group/phosphate ion
ChEBI 7091
29112
PubChem 440289
446894
1v5xA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1v5xB00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1dl3A00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1dl3B00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1lbmA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:137
1nsjA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [6]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1v5xA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 6;ASP 124
1v5xB00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 6;ASP 124
1dl3A00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 7;ASP 126
1dl3B00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 7;ASP 126
1lbmA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 7;ASP 126
1nsjA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 7;ASP 126

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[6]
Fig.4,p.12039

References
[1]
Resource
Comments
Medline ID
PubMed ID 8897600
Journal Protein Sci
Year 1996
Volume 5
Pages 2000-8
Authors Sterner R, Kleemann GR, Szadkowski H, Lustig A, Hennig M, Kirschner K
Title Phosphoribosyl anthranilate isomerase from Thermotoga maritima is an extremely stable and active homodimer.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9166771
Journal Biochemistry
Year 1997
Volume 36
Pages 6009-16
Authors Hennig M, Sterner R, Kirschner K, Jansonius JN
Title Crystal structure at 2.0 A resolution of phosphoribosyl anthranilate isomerase from the hyperthermophile Thermotoga maritima: possible determinants of protein stability.
Related PDB 1nsj
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 10944186
Journal Proc Natl Acad Sci U S A
Year 2000
Volume 97
Pages 9925-30
Authors Jurgens C, Strom A, Wegener D, Hettwer S, Wilmanns M, Sterner R
Title Directed evolution of a (beta alpha)8-barrel enzyme to catalyze related reactions in two different metabolic pathways.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 10745009
Journal Structure
Year 2000
Volume 8
Pages 265-76
Authors Thoma R, Hennig M, Sterner R, Kirschner K
Title Structure and function of mutationally generated monomers of dimeric phosphoribosylanthranilate isomerase from Thermotoga maritima.
Related PDB 1dl3
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 11551466
Journal Curr Opin Biotechnol
Year 2001
Volume 12
Pages 376-81
Authors Hocker B, Jurgens C, Wilmanns M, Sterner R
Title Stability, catalytic versatility and evolution of the (beta alpha)(8)-barrel fold.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 12356303
Journal Biochemistry
Year 2002
Volume 41
Pages 12032-42
Authors Henn-Sax M, Thoma R, Schmidt S, Hennig M, Kirschner K, Sterner R
Title Two (betaalpha)(8)-barrel enzymes of histidine and tryptophan biosynthesis have similar reaction mechanisms and common strategies for protecting their labile substrates.
Related PDB 1lbm
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 15857781
Journal Biomol Eng
Year 2005
Volume 22
Pages 31-8
Authors Hocker B
Title Directed evolution of (betaalpha)(8)-barrel enzymes.
Related PDB 1nsj
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 15944409
Journal J Biochem
Year 2005
Volume 137
Pages 569-78
Authors Taka J, Ogasahara K, Jeyakanthan J, Kunishima N, Kuroishi C, Sugahara M, Yokoyama S, Yutani K
Title Stabilization due to dimer formation of phosphoribosyl anthranilate isomerase from Thermus thermophilus HB8: X-ray Analysis and DSC experiments.
Related PDB 1v5x
Related UniProtKB

Comments
According to the literature [6], this enzyme catalyzes the following reactions:
(A) Eliminative double-bond formation; Intramolecular elimination leads to the Schiff-base intermediate formation:
(A1) Asp126 (of 1dl3) acts as a general acid to protonate the franose ring oxygen of the substrate, N-(5-phospho-beta-D-ribosyl)anthranilate (PRA), leading to the cleavage of the covalent bond between the oxygen and the C1' atom of the ring. This reaction yields a Schiff-base intermediate (I00057).
(B) Isomerization; Shift of double-bond position (from N=C-C to N-C=C), forming an enolamine intermediate:
(B1) Cys7 (of 1dl3) acts as a general base to deprotonate the C2' atom of the ribose, leading to the formation of an enolamine intermediate (I00058).
(C) Isomerization; Shift of double-bond position (from C=C-O to C-C=O), giving product:
(C0) This reaction might occur spontaneously, after the dissociation of the enolamine intermediate from the enzyme (see [6]).

Created Updated
2009-07-17 2010-03-05