DB code: S00226

RLCP classification 5.12.1497400.1 : Elimination
8.121.166300.1 : Isomerization
CATH domain 3.20.20.70 : TIM Barrel Catalytic domain
E.C. 5.3.1.16
CSA
M-CSA
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 S00847 S00224 S00225 D00014 D00029 M00141 T00015 T00239 D00664 D00665 D00804 D00863 T00089

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q9X0C7 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino] imidazole-4-carboxamide isomerase
EC 5.3.1.16
Phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase
NP_228843.1 (Protein)
NC_000853.1 (DNA/RNA sequence)
PF00977 (His_biosynth)
[Graphical View]

KEGG enzyme name
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamideisomerase
N-(5'-phospho-D-ribosylformimino)-5-amino-1-(5''-phosphoribosyl)-4-imidazolecarboxamide isomerase
phosphoribosylformiminoaminophosphoribosylimidazolecarboxamideisomerase
N-(phosphoribosylformimino) aminophosphoribosylimidazolecarboxamideisomerase
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamideketol-isomerase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q9X0C7 HIS4_THEMA 1-(5-phosphoribosyl)-5-((5- phosphoribosylamino)methylideneamino)imidazole-4-carboxamide = 5- ((5-phospho-1-deoxyribulos-1-ylamino)methylideneamino)-1-(5- phosphoribosyl)imidazole-4-carboxamide. Monomer. Cytoplasm (By similarity).

KEGG Pathways
Map code Pathways E.C.
MAP00340 Histidine metabolism

Compound table
Substrates Products Intermediates
KEGG-id C04896 C04916 I00059 I00060
E.C.
Compound 1-(5-Phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide 5-[(5-Phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide N'-[5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide-Schiff-base intermediate N'-[5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide
Type amide group,amine group,carbohydrate,imine group,nucleotide ,phosphate group/phosphate ion amide group,amine group,carbohydrate,imine group,nucleotide ,phosphate group/phosphate ion
ChEBI 18302
27735
PubChem 440534
5460212
9548599
193735
1qo2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1qo2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;Q9X0C7 & literature [6] and [9]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1qo2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 8;ASP 127
1qo2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 8;ASP 127

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[6]
Fig.4, p.12039-12040
[9]
Figure 3, p.876-877
[4]
p.1548-1549

References
[1]
Resource
Comments
Medline ID
PubMed ID 8433995
Journal Proc Natl Acad Sci U S A
Year 1993
Volume 90
Pages 1379-83
Authors Wilmanns M, Eisenberg D
Title Three-dimensional profiles from residue-pair preferences: identification of sequences with beta/alpha-barrel fold.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10413084
Journal FEBS Lett
Year 1999
Volume 454
Pages 1-6
Authors Thoma R, Obmolova G, Lang DA, Schwander M, Jeno P, Sterner R, Wilmanns M
Title Efficient expression, purification and crystallisation of two hyperthermostable enzymes of histidine biosynthesis.
Related PDB
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 X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS)
Medline ID 20425270
PubMed ID 10968789
Journal Science
Year 2000
Volume 289
Pages 1546-50
Authors Lang D, Thoma R, Henn-Sax M, Sterner R, Wilmanns M
Title Structural evidence for evolution of the beta/alpha barrel scaffold by gene duplication and fusion.
Related PDB 1qo2
Related UniProtKB Q9X0C7
[5]
Resource
Comments
Medline ID
PubMed ID 10991737
Journal Science
Year 2000
Volume 289
Pages 1490
Authors Miles EW, Davies DR
Title Protein evolution. On the ancestry of barrels.
Related PDB
Related UniProtKB
[6]
Resource
Comments ACTIVE SITES, SUBUNIT, AND MUTAGENESIS OF ASP-8; HIS-48; ASP-51; ARG-83; ASP-127 AND THR-164.
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
Related UniProtKB Q9X0C7
[7]
Resource
Comments
Medline ID
PubMed ID 12206759
Journal J Mol Biol
Year 2002
Volume 321
Pages 741-65
Authors Nagano N, Orengo CA, Thornton JM
Title One fold with many functions: the evolutionary relationships between TIM barrel families based on their sequences, structures and functions.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 12634849
Journal EMBO Rep
Year 2003
Volume 4
Pages 296-300
Authors Barona-Gomez F, Hodgson DA
Title Occurrence of a putative ancient-like isomerase involved in histidine and tryptophan biosynthesis.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 15033357
Journal J Mol Biol
Year 2004
Volume 337
Pages 871-9
Authors Leopoldseder S, Claren J, Jurgens C, Sterner R
Title Interconverting the catalytic activities of (betaalpha)(8)-barrel enzymes from different metabolic pathways: sequence requirements and molecular analysis.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 15539462
Journal Proc Natl Acad Sci U S A
Year 2004
Volume 101
Pages 16448-53
Authors Hocker B, Claren J, Sterner R
Title Mimicking enzyme evolution by generating new (betaalpha)8-barrels from (betaalpha)4-half-barrels.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 15654319
Journal EMBO Rep
Year 2005
Volume 6
Pages 134-9
Authors Kuper J, Doenges C, Wilmanns M
Title Two-fold repeated (betaalpha)4 half-barrels may provide a molecular tool for dual substrate specificity.
Related PDB
Related UniProtKB

Comments
According to the literature [6] and [9], this enzyme catalyzes the following reactions:
(A) Eliminative double-bond formation; Intramolecular elimination leads to the Schiff-base intermediate formation:
(A1) Asp127 acts as a general acid to protonate the franose ring oxygen of the substrate, ProFAR (C04896), 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 (I00059).
(B) Isomerization; Shift of double-bond position (from N=C-C to N-C=C), forming an enolamine intermediate:
(B1) Asp8 acts as a general base to deprotonate the C2' atom of the ribose, leading to the formation of an enolamine intermediate (I00060).
(C) Isomerization; Shift of double-bond position (from C=C-O to C-C=O), giving product:

Created Updated
2004-04-07 2010-03-05