EzCatDB: S00826
Related links:    PDB-formatted query search system Fasta-formatted query search system Fasta-formatted query search system

DB codeS00826
RLCP classification4.191.350400.117 : Addition
5.125.526200.114 : Elimination
5.10.552200.114 : Elimination
CATH domainDomain 13.20.20.70 : TIM BarrelCatalytic domain
E.C.4.1.1.48
MACiEM0252

CATH domainRelated DB codes (homologues)
3.20.20.70 : TIM BarrelS00215,S00217,S00218,S00219,S00532,S00198,S00220,S00745,S00537,S00538,S00539,S00841,S00235,S00239,S00240,S00243,S00244,S00199,S00200,S00201,S00221,S00222,S00847,S00224,S00225,S00226,D00014,D00029,M00141,T00015,T00239,D00664,D00665,D00804,D00863,T00089

Enzyme Name
UniProtKBKEGG

Q06121Q56319P84126
Protein nameIndole-3-glycerol phosphate synthaseIndole-3-glycerol phosphate synthase
indole-3-glycerol-phosphate synthase
indoleglycerol phosphate synthetase
indoleglycerol phosphate synthase
indole-3-glycerophosphate synthase
1-(2-carboxyphenylamino)-1-deoxy-D-ribulose-5-phosphate carboxy-lyase (cyclizing)
SynonymsIGPS
EC 4.1.1.48
IGPS
EC 4.1.1.48
Indole-3-glycerol phosphate synthase
EC 4.1.1.48
RefSeqNP_342387.1 (Protein)
NC_002754.1 (DNA/RNA sequence)
NP_227955.1 (Protein)
NC_000853.1 (DNA/RNA sequence)

PfamPF00218 (IGPS)
[Graphical view]
PF00218 (IGPS)
[Graphical view]
PF00218 (IGPS)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00400Phenylalanine, tyrosine and tryptophan biosynthesis
MAP02020Two-component system - General

UniProtKB:Accession NumberQ06121Q56319P84126
Entry nameTRPC_SULSOTRPC_THEMAP84126_THETH
Activity1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate = C(1)-(3-indolyl)-glycerol 3-phosphate + CO(2) + H(2)O.1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate = C(1)-(3-indolyl)-glycerol 3-phosphate + CO(2) + H(2)O.
SubunitMonomer.

Subcellular location


Cofactor



Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC01302C03506C00011C00001I00053I00054
Compound1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate1-C-(indol-3-yl)glycerol 3-phosphateCO2H2OCdRP intermediate I1CdRP intermediate I2
Typeamine group,aromatic ring (only carbon atom),carbohydrate,carboxyl group,phosphate group/phosphate ionaromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,phosphate group/phosphate ionothersH2O

ChEBI29112
51793
16526
15377


PubChem446894
444150
280
962
22247451


              
1a53AUnboundBound:IGPUnbound UnboundUnbound
1igsAUnboundUnboundUnbound UnboundUnbound
1jukAUnboundUnboundUnbound UnboundUnbound
1julAUnboundUnboundUnbound UnboundUnbound
1lbfAAnalogue:137UnboundUnbound UnboundUnbound
1lblAAnalogue:137UnboundUnbound UnboundUnbound
2c3zAUnboundUnboundUnbound UnboundUnbound
1i4nAUnboundUnboundUnbound UnboundUnbound
1i4nBUnboundUnboundUnbound UnboundUnbound
1j5tAUnboundUnboundUnbound UnboundUnbound
1vc4AUnboundUnboundUnbound UnboundUnbound
1vc4BUnboundUnboundUnbound UnboundUnbound

Active-site residues
resource
literature [24], [28]
pdbCatalytic residuescomment
          
1a53AGLU 51;LYS 53;LYS 110;GLU 159;ASN 180;GLU 210;SER 211
 
1igsAGLU 51;LYS 53;LYS 110;GLU 159;ASN 180;GLU 210;SER 211
 
1jukAGLU 51;LYS 53;LYS 110;GLU 159;ASN 180;GLU 210;SER 211
 
1julAGLU 51;LYS 53;LYS 110;GLU 159;ASN 180;GLU 210;SER 211
 
1lbfAGLU 51;LYS 53;LYS 110;GLU 159;ASN 180;GLU 210;SER 211
 
1lblAGLU 51;LYS 53;LYS 110;GLU 159;ASN 180;GLU 210;SER 211
 
2c3zAGLU 51;LYS 53;LYS 110;GLU 159;ASN 180;GLU 210;SER 211
deletion 1-26
1i4nAGLU 47;LYS 49;LYS 108;GLU 157;ASN 179;GLU 209;SER 210
 
1i4nBGLU 47;LYS 49;LYS 108;GLU 157;ASN 179;GLU 209;SER 210
 
1j5tAGLU 25;LYS 27;LYS  86;GLU 135;ASN 157;GLU 187;SER 188
 
1vc4AGLU 51;LYS 53;LYS 112;GLU 160;ASN 181;GLU 214;SER 215
 
1vc4BGLU 51;LYS 53;LYS 112;GLU 160;ASN 181;GLU 214;SER 215
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]p.221
[8]p.499
[18]Fig.2, p.1227-1229
[24]Fig.6, p.764
[27]

[28]Scheme 2, p.14381-14383

references
[1]
PubMed ID3303031
JournalProc Natl Acad Sci U S A
Year1987
Volume84
Pages5690-4
AuthorsPriestle JP, Gr?tter MG, White JL, Vincent MG, Kania M, Wilson E, Jardetzky TS, Kirschner K, Jansonius JN
TitleThree-dimensional structure of the bifunctional enzyme N-(5'-phosphoribosyl)anthranilate isomerase-indole-3-glycerol-phosphate synthase from Escherichia coli.
[2]
PubMed ID2494074
JournalFEBS Lett
Year1989
Volume245
Pages219-22
AuthorsEberhard M, Kirschner K
TitleModification of a catalytically important residue of indoleglycerol-phosphate synthase from Escherichia coli.
[3]
PubMed ID2184433
JournalProtein Eng
Year1990
Volume3
Pages173-80
AuthorsWilmanns M, Schlagenhauf E, Fol B, Jansonius JN
TitleCrystallization and structure solution at 4 A resolution of the recombinant synthase domain of N-(5'-phosphoribosyl)anthranilate isomerase:indole-3-glycerol-phosphate synthase from Escherichia coli complexed to a substrate analogue.
[4]
PubMed ID1857718
JournalProtein Eng
Year1991
Volume4
Pages359-70
AuthorsNiermann T, Kirschner K
TitleImproving the prediction of secondary structure of 'TIM-barrel' enzymes.
[5]
PubMed ID1892826
JournalBiochemistry
Year1991
Volume30
Pages9161-9
AuthorsWilmanns M, Hyde CC, Davies DR, Kirschner K, Jansonius JN
TitleStructural conservation in parallel beta/alpha-barrel enzymes that catalyze three sequential reactions in the pathway of tryptophan biosynthesis.
[6]
PubMed ID1374562
JournalProteins
Year1992
Volume12
Pages299-313
AuthorsScheerlinck JP, Lasters I, Claessens M, De Maeyer M, Pio F, Delhaise P, Wodak SJ
TitleRecurrent alpha beta loop structures in TIM barrel motifs show a distinct pattern of conserved structural features.
[7]
PubMed ID1567820
JournalBiochemistry
Year1992
Volume31
Pages3617-25
AuthorsEder J, Kirschner K
TitleStable substructures of eightfold beta alpha-barrel proteins: fragment complementation of phosphoribosylanthranilate isomerase.
[8]
PubMed ID1738159
JournalJ Mol Biol
Year1992
Volume223
Pages477-507
AuthorsWilmanns M, Priestle JP, Niermann T, Jansonius JN
TitleThree-dimensional structure of the bifunctional enzyme phosphoribosylanthranilate isomerase: indoleglycerolphosphate synthase from Escherichia coli refined at 2.0 A resolution.
[9]
PubMed ID7947963
JournalBiochim Biophys Acta
Year1994
Volume1208
Pages310-5
AuthorsAndreotti G, Tutino ML, Sannia G, Marino G, Cubellis MV
TitleIndole-3-glycerol-phosphate synthase from Sulfolobus solfataricus as a model for studying thermostable TIM-barrel enzymes.
[10]
PubMed ID8001582
JournalEur J Biochem
Year1994
Volume226
Pages657-64
AuthorsCrombie T, Boyle JP, Coggins JR, Brown AJ
TitleThe folding of the bifunctional TRP3 protein in yeast is influenced by a translational pause which lies in a region of structural divergence with Escherichia coli indoleglycerol-phosphate synthase.
[11]
PubMed ID7556082
JournalEMBO J
Year1995
Volume14
Pages4395-402
AuthorsSterner R, Dahm A, Darimont B, Ivens A, Liebl W, Kirschner K
Title(Beta alpha)8-barrel proteins of tryptophan biosynthesis in the hyperthermophile Thermotoga maritima.
[12]
PubMed ID8747452
JournalStructure
Year1995
Volume3
Pages1277-9
AuthorsGoldman A
TitleHow to make my blood boil.
[13]
PubMed ID8747456
JournalStructure
Year1995
Volume3
Pages1295-306
AuthorsHennig M, Darimont B, Sterner R, Kirschner K, Jansonius JN
Title2.0 A structure of indole-3-glycerol phosphate synthase from the hyperthermophile Sulfolobus solfataricus: possible determinants of protein stability.
Related PDB1igs
[14]
PubMed ID8893859
JournalJ Mol Biol
Year1996
Volume262
Pages502-15
AuthorsKn?chel TR, Hennig M, Merz A, Darimont B, Kirschner K, Jansonius JN
TitleThe crystal structure of indole-3-glycerol phosphate synthase from the hyperthermophilic archaeon Sulfolobus solfataricus in three different crystal forms: effects of ionic strength.
Related PDB1juk,1jul
[15]
PubMed ID9091315
JournalFEBS Lett
Year1997
Volume403
Pages268-72
AuthorsStehlin C, Dahm A, Kirschner K
TitleDeletion mutagenesis as a test of evolutionary relatedness of indoleglycerol phosphate synthase with other TIM barrel enzymes.
[16]
PubMed ID9154940
JournalBiochemistry
Year1997
Volume36
Pages5560-5
AuthorsS?nchez del Pino MM, Fersht AR
TitleNonsequential unfolding of the alpha/beta barrel protein indole-3-glycerol-phosphate synthase.
[17]
PubMed ID9173891
JournalBiochem J
Year1997
Volume323
Pages259-64
AuthorsAndreotti G, Cubellis MV, Palo MD, Fessas D, Sannia G, Marino G
TitleStability of a thermophilic TIM-barrel enzyme: indole-3-glycerol phosphate synthase from the thermophilic archaeon Sulfolobus solfataricus.
[18]
PubMed ID9605328
JournalProtein Sci
Year1998
Volume7
Pages1221-32
AuthorsDarimont B, Stehlin C, Szadkowski H, Kirschner K
TitleMutational analysis of the active site of indoleglycerol phosphate synthase from Escherichia coli.
[19]
PubMed ID10653631
JournalBiochemistry
Year2000
Volume39
Pages880-9
AuthorsMerz A, Yee MC, Szadkowski H, Pappenberger G, Crameri A, Stemmer WP, Yanofsky C, Kirschner K
TitleImproving the catalytic activity of a thermophilic enzyme at low temperatures.
[20]
PubMed ID10700266
JournalNat Struct Biol
Year2000
Volume7
Pages171-3
AuthorsGerlt JA
TitleNew wine from old barrels.
[21]
PubMed ID10715203
JournalJ Mol Biol
Year2000
Volume297
Pages309-19
AuthorsCho G, Keefe AD, Liu R, Wilson DS, Szostak JW
TitleConstructing high complexity synthetic libraries of long ORFs using in vitro selection.
[22]
PubMed ID11741953
JournalJ Biol Chem
Year2002
Volume277
Pages8626-34
AuthorsKn?chel T, Pappenberger A, Jansonius JN, Kirschner K
TitleThe crystal structure of indoleglycerol-phosphate synthase from Thermotoga maritima. Kinetic stabilization by salt bridges.
Related PDB1i4n
[23]
PubMed ID11856350
JournalEur J Biochem
Year2002
Volume269
Pages1145-53
AuthorsIvens A, Mayans O, Szadkowski H, J?rgens C, Wilmanns M, Kirschner K
TitleStabilization of a (betaalpha)8-barrel protein by an engineered disulfide bridge.
[24]
PubMed ID12054868
JournalJ Mol Biol
Year2002
Volume319
Pages757-66
AuthorsHennig M, Darimont BD, Jansonius JN, Kirschner K
TitleThe catalytic mechanism of indole-3-glycerol phosphate synthase: crystal structures of complexes of the enzyme from Sulfolobus solfataricus with substrate analogue, substrate, and product.
Related PDB1a53,1lbf,1lbl
[25]
PubMed ID12686139
JournalBiochim Biophys Acta
Year2003
Volume1647
Pages234-8
AuthorsDenesyuk AI, Denessiouk KA, Korpela T, Johnson MS
TitlePhosphate group binding cup of PLP-dependent and non-PLP-dependent enzymes: leitmotif and variations.
[26]
PubMed ID15110684
JournalPhytochemistry
Year2004
Volume65
Pages1047-55
AuthorsFrey M, Spiteller D, Boland W, Gierl A
TitleTranscriptional activation of Igl, the gene for indole formation in Zea mays: a structure-activity study with elicitor-active N-acyl glutamines from insects.
[27]
PubMed ID15137737
JournalJ Am Chem Soc
Year2004
Volume126
Pages5936-7
AuthorsMazumder-Shivakumar D, Kahn K, Bruice TC
TitleComputational study of the ground state of thermophilic indole glycerol phosphate synthase: structural alterations at the active site with temperature.
[28]
PubMed ID15452341
JournalProc Natl Acad Sci U S A
Year2004
Volume101
Pages14379-84
AuthorsMazumder-Shivakumar D, Bruice TC
TitleMolecular dynamics studies of ground state and intermediate of the hyperthermophilic indole-3-glycerol phosphate synthase.
[29]
PubMed ID16342933
JournalBiochemistry
Year2005
Volume44
Pages16405-12
AuthorsSchneider B, Kn?chel T, Darimont B, Hennig M, Dietrich S, Babinger K, Kirschner K, Sterner R
TitleRole of the N-terminal extension of the (betaalpha)8-barrel enzyme indole-3-glycerol phosphate synthase for its fold, stability, and catalytic activity.
Related PDB2c3z
[30]
PubMed ID16487066
JournalBiochemistry (Mosc)
Year2006
Volume71
PagesS38-43
AuthorsYang Y, Zhang M, Zhang H, Lei J, Jin R, Xu S, Bao J, Zhang L, Wang H
TitlePurification and characterization of Mycobacterium tuberculosis indole-3-glycerol
[31]
PubMed ID17359995
JournalJ Mol Biol
Year2007
Volume368
Pages582-94
AuthorsGu Z, Zitzewitz JA, Matthews CR
TitleMapping the structure of folding cores in TIM barrel proteins by hydrogen exchange mass spectrometry: the roles of motif and sequence for the indole-3-glycerol phosphate synthase from Sulfolobus solfataricus.
[32]
PubMed ID19032598
JournalFEBS J
Year2009
Volume276
Pages144-54
AuthorsShen H, Wang F, Zhang Y, Huang Q, Xu S, Hu H, Yue J, Wang H
TitleA novel inhibitor of indole-3-glycerol phosphate synthase with activity against multidrug-resistant Mycobacterium tuberculosis.
[33]
PubMed ID19364491
JournalArch Biochem Biophys
Year2009
Volume486
Pages19-26
AuthorsCzekster CM, Neto BA, Lapis AA, Dupont J, Santos DS, Basso LA
TitleSteady-state kinetics of indole-3-glycerol phosphate synthase from Mycobacterium tuberculosis.

comments
This enzyme catalyzes the following reaction, which should be divided into three basic reactions, according to the literature [24] and [28]:
(A) Addition of benzen to carbonyl group, leading to intermediate I1 (see [24]):
(A1) Lys110 acts (of 1a53) as a general acid to protonate the C2' carbonyl oxygen of substrate (protonation site), CdRP, leading to the polarization of the C2' carbon (addition site).
(A2) The electrophilic C2' atom makes an attack on the pi electrons of the benzen ring (added group).
(A3) Meanwhile, Lys53 modulates the distance between C1 atom and C2' atom, by interacting with the anthranilate carboxylate.
(A4) Glu159 stabilizes the positive charge developing on the amine group of the substrate, during the formation of the imine from the amine group.
(A5) Lys53 and Glu51 mediate the reprotonation of Lys110.
(B) Elimination of CO2 (decarboxylation) from intermediate I1 to form intermediate I2 (see [24]):
(B0) Glu159 stabilizes the positive charge on the imine group.
(B1) Lys53 modulates the electrons on the leaving carboxylate group, leading to the pi-electron restoration and neutralization of the positive charge on the imine group. Thus, the amine group recovers from the imine group, leading to intermediate I2.
(B2) This elimination reaction might be E1cB-like.
(C) Elimination of H2O(dehydration) from intermediate I2 to form product (see [28]):
(C1) Lys110 acts as a general acid to protonate the eliminated hydroxyl group.
(C2) Glu210 acts as a genral base to the C1' proton.
(C3) This elimination reaction might be E2-like reaction.
(C4) In the end, proton transfer from Glu210 to Lys110, to restore the activities of these catalytic residues.

createdupdated
2009-07-242009-07-27


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.