DB code: S00847

RLCP classification	5.12.1497400.1 : Elimination
RLCP classification	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 7091	29112 29112
PubChem	440289 440289	446894 446894

1v5xA00	Unbound	Unbound
1v5xB00	Unbound	Unbound
1dl3A00	Unbound	Unbound
1dl3B00	Unbound	Unbound
1lbmA00	Unbound	Analogue:137
1nsjA00	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	CYS 6;ASP 124
1v5xB00	CYS 6;ASP 124
1dl3A00	CYS 7;ASP 126
1dl3B00	CYS 7;ASP 126
1lbmA00	CYS 7;ASP 126
1nsjA00	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]).

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