EzCatDB: S00226
Related links:    PDB-formatted query search system Fasta-formatted query search system Fasta-formatted query search system

DB codeS00226
RLCP classification5.12.1497400.1 : Elimination
8.121.166300.1 : Isomerization
CATH domainDomain 13.20.20.70 : TIM BarrelCatalytic domain
E.C.5.3.1.16

CATH domainRelated DB codes (homologues)
3.20.20.70 : TIM BarrelS00215,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

Enzyme Name
UniProtKBKEGG

Q9X0C7
Protein name1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino] imidazole-4-carboxamide isomerase1-(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
SynonymsEC 5.3.1.16
Phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase
RefSeqNP_228843.1 (Protein)
NC_000853.1 (DNA/RNA sequence)
PfamPF00977 (His_biosynth)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00340Histidine metabolism

UniProtKB:Accession NumberQ9X0C7
Entry nameHIS4_THEMA
Activity1-(5-phosphoribosyl)-5-((5- phosphoribosylamino)methylideneamino)imidazole-4-carboxamide = 5- ((5-phospho-1-deoxyribulos-1-ylamino)methylideneamino)-1-(5- phosphoribosyl)imidazole-4-carboxamide.
SubunitMonomer.
Subcellular locationCytoplasm (By similarity).
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC04896C04916I00059I00060
Compound1-(5-Phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide5-[(5-Phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamideN'-[5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide-Schiff-base intermediateN'-[5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide
Typeamide group,amine group,carbohydrate,imine group,nucleotide,phosphate group/phosphate ionamide group,amine group,carbohydrate,imine group,nucleotide,phosphate group/phosphate ion

ChEBI18302
27735


PubChem9548599
5460212
440534
193735


            
1qo2AUnboundUnbound  
1qo2BUnboundUnbound  

Active-site residues
resource
Swiss-prot;Q9X0C7 & literature [6] and [9]
pdbCatalytic residues
         
1qo2AASP 8;ASP 127
1qo2BASP 8;ASP 127

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]p.1548-1549
[6]Fig.4, p.12039-12040
[9]Figure 3, p.876-877

references
[1]
PubMed ID8433995
JournalProc Natl Acad Sci U S A
Year1993
Volume90
Pages1379-83
AuthorsWilmanns M, Eisenberg D
TitleThree-dimensional profiles from residue-pair preferences: identification of sequences with beta/alpha-barrel fold.
[2]
PubMed ID10413084
JournalFEBS Lett
Year1999
Volume454
Pages1-6
AuthorsThoma R, Obmolova G, Lang DA, Schwander M, Jeno P, Sterner R, Wilmanns M
TitleEfficient expression, purification and crystallisation of two hyperthermostable enzymes of histidine biosynthesis.
[3]
PubMed ID10944186
JournalProc Natl Acad Sci U S A
Year2000
Volume97
Pages9925-30
AuthorsJurgens C, Strom A, Wegener D, Hettwer S, Wilmanns M, Sterner R
TitleDirected evolution of a (beta alpha)8-barrel enzyme to catalyze related reactions in two different metabolic pathways.
[4]
CommentsX-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS)
Medline ID20425270
PubMed ID10968789
JournalScience
Year2000
Volume289
Pages1546-50
AuthorsLang D, Thoma R, Henn-Sax M, Sterner R, Wilmanns M
TitleStructural evidence for evolution of the beta/alpha barrel scaffold by gene duplication and fusion.
Related PDB1qo2
Related UniProtKBQ9X0C7
[5]
PubMed ID10991737
JournalScience
Year2000
Volume289
Pages1490
AuthorsMiles EW, Davies DR
TitleProtein evolution. On the ancestry of barrels.
[6]
CommentsACTIVE SITES, SUBUNIT, AND MUTAGENESIS OF ASP-8; HIS-48; ASP-51; ARG-83; ASP-127 AND THR-164.
PubMed ID12356303
JournalBiochemistry
Year2002
Volume41
Pages12032-42
AuthorsHenn-Sax M, Thoma R, Schmidt S, Hennig M, Kirschner K, Sterner R
TitleTwo (betaalpha)(8)-barrel enzymes of histidine and tryptophan biosynthesis have similar reaction mechanisms and common strategies for protecting their labile substrates.
Related UniProtKBQ9X0C7
[7]
PubMed ID12206759
JournalJ Mol Biol
Year2002
Volume321
Pages741-65
AuthorsNagano N, Orengo CA, Thornton JM
TitleOne fold with many functions: the evolutionary relationships between TIM barrel families based on their sequences, structures and functions.
[8]
PubMed ID12634849
JournalEMBO Rep
Year2003
Volume4
Pages296-300
AuthorsBarona-Gomez F, Hodgson DA
TitleOccurrence of a putative ancient-like isomerase involved in histidine and tryptophan biosynthesis.
[9]
PubMed ID15033357
JournalJ Mol Biol
Year2004
Volume337
Pages871-9
AuthorsLeopoldseder S, Claren J, Jurgens C, Sterner R
TitleInterconverting the catalytic activities of (betaalpha)(8)-barrel enzymes from different metabolic pathways: sequence requirements and molecular analysis.
[10]
PubMed ID15539462
JournalProc Natl Acad Sci U S A
Year2004
Volume101
Pages16448-53
AuthorsHocker B, Claren J, Sterner R
TitleMimicking enzyme evolution by generating new (betaalpha)8-barrels from (betaalpha)4-half-barrels.
[11]
PubMed ID15654319
JournalEMBO Rep
Year2005
Volume6
Pages134-9
AuthorsKuper J, Doenges C, Wilmanns M
TitleTwo-fold repeated (betaalpha)4 half-barrels may provide a molecular tool for dual substrate specificity.

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:

createdupdated
2004-04-072010-03-05


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
© Biotechnology Research Institute for Drug Discovery, AIST, 2015-2016 All Rights Reserved.
© Computational Biology Research Center, AIST, 2004-2016 All Rights Reserved.