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Escherichia coli K-12 substr. MG1655 Enzyme: isopentenyl diphosphate isomerase



Gene: idi Accession Numbers: G7508 (EcoCyc), b2889, ECK2884

Synonyms: ygfV

Regulation Summary Diagram: ?

Summary:
Isopentenyl diphosphate (IPP) isomerase (Idi) catalyzes the reversible isomerization of isopentenyl diphosphate (IPP) to dimethylallyl diphosphate (DMAPP), a key step in the biosynthesis of isoprenoids.

Idi catalyzes the reversible isomerization of IPP to DMAPP [Fujisaki86, Hahn99, RodriguezConcep00]. The initial 5-6:1 ratio of IPP to DMAPP generated by 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase is adjusted to a final ratio of 3:7 by Idi [Rohdich03].

The enzyme requires two divalent cations for activity; a Zn2+ ion is located in a hexacoordinate His3Glu2 pocket and is part of the catalytic machinery, while the enzyme-substrate complex contains an additional Mg2+ ion that facilitates substrate binding. A wide variety of divalent metal ions can provide these functions [Lee06d].

Crystal structures of free and metal-bound isopentenyl diphosphate isomerase enabled identification of the active site [Durbecq01]. Crystal structures of complexes with transition state analogues and irreversible inhibitors suggested a catalytic mechanism of protonation/deprotonation involving C67 and E116 [Wouters03a, Wu05d], and crystal structures of site-directed mutants in C67 were obtained to confirm the proposed mechanism [Wouters04]. Crystal structures of isopentenyl diphosphate isomerase together with the bromohydrin of IPP, an inhibitor of the enzyme, show covalent adducts of C67 and E116 [Wouters05]. Crystal structures of mutants in the Y104 residue demonstrate its role in folding of IPP isomerase [deRuyck06]. The structure of isopentenyl diphosphate isomerase shows similarity to the Nudix hydrolases [Bonanno01].

E. coli isopentenyl diphosphate isomerase is a Type I enzyme. In contrast, Type II isopentenyl diphosphate isomerases are structurally unrelated and require reduced FMN and Mg2+ for activity [Sharma10].

Isotope exchange studies of the reaction mechanism resulted in a proposal that ligand binding to the enzyme is relatively slow. This is due to a significant kinetic barrier to reorganization of the initial encounter complex between enzyme, substrate, and Mg2+ to form the Michaelis complex where the metal cation bridges the protein and the substrate diphosphate group [Jonnalagadda12].

In metabolic engineering studies, co-expression of the idi gene was useful in increasing the production of lycopene [Jin07] and prenyl alcohols [Ohto09] in E. coli.

idi is not essential for growth [Hahn99].

Gene Citations: [Hemmi98]

Locations: cytosol

Map Position: [3,031,087 -> 3,031,635] (65.33 centisomes)
Length: 549 bp / 182 aa

Molecular Weight of Polypeptide: 20.508 kD (from nucleotide sequence), 20.5 kD (experimental) [Hahn99 ]

Unification Links: ASAP:ABE-0009484 , EchoBASE:EB2883 , EcoGene:EG13072 , EcoliWiki:b2889 , ModBase:Q46822 , OU-Microarray:b2889 , PortEco:idi , PR:PRO_000022992 , Protein Model Portal:Q46822 , RefSeq:NP_417365 , RegulonDB:G7508 , SMR:Q46822 , String:511145.b2889 , UniProt:Q46822

Relationship Links: InterPro:IN-FAMILY:IPR000086 , InterPro:IN-FAMILY:IPR011876 , InterPro:IN-FAMILY:IPR015797 , Panther:IN-FAMILY:PTHR10885 , PDB:Structure:1HX3 , PDB:Structure:1HZT , PDB:Structure:1I9A , PDB:Structure:1NFS , PDB:Structure:1NFZ , PDB:Structure:1OW2 , PDB:Structure:1PPV , PDB:Structure:1PPW , PDB:Structure:1PVF , PDB:Structure:1Q54 , PDB:Structure:1R67 , PDB:Structure:1X83 , PDB:Structure:1X84 , PDB:Structure:2B2K , PDB:Structure:2G73 , PDB:Structure:2G74 , PDB:Structure:2VNP , PDB:Structure:2VNQ , Pfam:IN-FAMILY:PF00293 , Prosite:IN-FAMILY:PS51462

In Paralogous Gene Group: 33 (6 members)

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0006744 - ubiquinone biosynthetic process Inferred from experiment [Hahn99]
GO:0006974 - cellular response to DNA damage stimulus Inferred from experiment [Khil02]
GO:0008299 - isoprenoid biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA06, GOA01, Sherman89]
GO:0050992 - dimethylallyl diphosphate biosynthetic process Inferred by computational analysis [UniProtGOA12]
Molecular Function: GO:0004452 - isopentenyl-diphosphate delta-isomerase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Hahn99]
GO:0016787 - hydrolase activity Inferred by computational analysis [GOA01]
GO:0016853 - isomerase activity Inferred by computational analysis [UniProtGOA11]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, GOA06]
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism biosynthesis of building blocks cofactors, small molecule carriers menaquinone, ubiquinone

Essentiality data for idi knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Credits:
Curated 12-Sep-2006 by Keseler I , SRI International
Curated 14-May-2007 by Shearer A , SRI International
Last-Curated ? 22-Mar-2013 by Fulcher C , SRI International


Enzymatic reaction of: isopentenyl diphosphate isomerase

Synonyms: IPP isomerase, isopentenyl pyrophosphate isomerase, isopentenyl diphosphate δ-isomerase, isopentenyl diphosphate δ3-δ2-isomerase, dimethylallyl diphosphate isomerase, isopentenyl pyrophosphate/dimethylallyl pyrophosphate isomerase

EC Number: 5.3.3.2

isopentenyl diphosphate <=> dimethylallyl diphosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

This reaction is reversible. [Hahn99]

In Pathways: polyisoprenoid biosynthesis (E. coli) , trans, trans-farnesyl diphosphate biosynthesis , methylerythritol phosphate pathway I

Cofactors or Prosthetic Groups [Comment 5]: Zn2+ [Carrigan03], Mg2+ [Hahn99]

Alternative Cofactors for Mg2+: Mn2+ [Comment 6 ]

Inhibitors (Unknown Mechanism): iodoacetamide [Fujisaki86, Comment 7] , bromohydrin of isopentenyl pyrophosphate [Wouters03]

Kinetic Parameters:

Substrate
Km (μM)
Citations
dimethylallyl diphosphate
14.3
[Hahn99]
isopentenyl diphosphate
9.5
[deRuyck06, BRENDA14]
isopentenyl diphosphate
3.5
[Durbecq01]


Sequence Features

Feature Class Location Citations Comment
Amino-Acid-Sites-That-Bind 21
[UniProt10a]
UniProt: Substrate;
Metal-Binding-Site 25
[UniProt10a]
UniProt: Manganese;
Conserved-Region 30 -> 164
[UniProt09]
UniProt: Nudix hydrolase;
Metal-Binding-Site 32
[UniProt10a]
UniProt: Manganese;
Amino-Acid-Sites-That-Bind 51
[UniProt10a]
UniProt: Substrate;
Amino-Acid-Sites-That-Bind 55
[UniProt10a]
UniProt: Substrate;
Metal-Binding-Site 67
[UniProt10a]
UniProt: Magnesium; via carbonyl oxygen;
Active-Site 67
[UniProt10a]
Metal-Binding-Site 69
[UniProt10a]
UniProt: Manganese;
Amino-Acid-Sites-That-Bind 83
[UniProt10a]
UniProt: Substrate;
Metal-Binding-Site 87
[UniProt10a]
UniProt: Magnesium;
Mutagenesis-Variant 104
[UniProt10a]
Alternate sequence: Y → F; UniProt: Reduces activity by 97%;
Alternate sequence: Y → A; UniProt: Reduces activity by 99%;
Amino-Acid-Site 104
[UniProt10a]
UniProt: Essential for catalytic activity; Sequence Annotation Type: site;
Metal-Binding-Site 114
[UniProt10a]
UniProt: Manganese;
Metal-Binding-Site 116
[UniProt10a]
UniProt: Manganese;
Active-Site 116
[UniProt10a]


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


References

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Bonanno01: Bonanno JB, Edo C, Eswar N, Pieper U, Romanowski MJ, Ilyin V, Gerchman SE, Kycia H, Studier FW, Sali A, Burley SK (2001). "Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis." Proc Natl Acad Sci U S A 98(23);12896-901. PMID: 11698677

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Carrigan03: Carrigan CN, Poulter CD (2003). "Zinc is an essential cofactor for type I isopentenyl diphosphate:dimethylallyl diphosphate isomerase." J Am Chem Soc 125(30);9008-9. PMID: 15369345

deRuyck06: de Ruyck J, Durisotti V, Oudjama Y, Wouters J (2006). "Structural role for Tyr-104 in Escherichia coli isopentenyl-diphosphate isomerase: site-directed mutagenesis, enzymology, and protein crystallography." J Biol Chem 281(26);17864-9. PMID: 16617181

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Durbecq01: Durbecq V, Sainz G, Oudjama Y, Clantin B, Bompard-Gilles C, Tricot C, Caillet J, Stalon V, Droogmans L, Villeret V (2001). "Crystal structure of isopentenyl diphosphate:dimethylallyl diphosphate isomerase." EMBO J 20(7);1530-7. PMID: 11285217

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Fujisaki86: Fujisaki S, Nishino T, Katsuki H (1986). "Isoprenoid synthesis in Escherichia coli. Separation and partial purification of four enzymes involved in the synthesis." J Biochem (Tokyo) 1986;99(5);1327-37. PMID: 3519603

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Hahn99: Hahn FM, Hurlburt AP, Poulter CD (1999). "Escherichia coli open reading frame 696 is idi, a nonessential gene encoding isopentenyl diphosphate isomerase." J Bacteriol 1999;181(15);4499-504. PMID: 10419945

Hemmi98: Hemmi H, Ohnuma S, Nagaoka K, Nishino T (1998). "Identification of genes affecting lycopene formation in Escherichia coli transformed with carotenoid biosynthetic genes: candidates for early genes in isoprenoid biosynthesis." J Biochem (Tokyo) 123(6);1088-96. PMID: 9603997

Jin07: Jin YS, Stephanopoulos G (2007). "Multi-dimensional gene target search for improving lycopene biosynthesis in Escherichia coli." Metab Eng 9(4);337-47. PMID: 17509919

Jonnalagadda12: Jonnalagadda V, Toth K, Richard JP (2012). "Isopentenyl diphosphate isomerase catalyzed reactions in D2O: product release limits the rate of this sluggish enzyme-catalyzed reaction." J Am Chem Soc 134(15);6568-70. PMID: 22471428

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Khil02: Khil PP, Camerini-Otero RD (2002). "Over 1000 genes are involved in the DNA damage response of Escherichia coli." Mol Microbiol 44(1);89-105. PMID: 11967071

Lee06d: Lee S, Poulter CD (2006). "Escherichia coli type I isopentenyl diphosphate isomerase: structural and catalytic roles for divalent metals." J Am Chem Soc 128(35);11545-50. PMID: 16939278

Ohto09: Ohto C, Muramatsu M, Obata S, Sakuradani E, Shimizu S (2009). "Prenyl alcohol production by expression of exogenous isopentenyl diphosphate isomerase and farnesyl diphosphate synthase genes in Escherichia coli." Biosci Biotechnol Biochem 73(1);186-8. PMID: 19129660

RodriguezConcep00: Rodriguez-Concepcion M, Campos N, Maria Lois L, Maldonado C, Hoeffler JF, Grosdemange-Billiard C, Rohmer M, Boronat A (2000). "Genetic evidence of branching in the isoprenoid pathway for the production of isopentenyl diphosphate and dimethylallyl diphosphate in Escherichia coli." FEBS Lett 2000;473(3);328-32. PMID: 10818234

Rohdich03: Rohdich F, Zepeck F, Adam P, Hecht S, Kaiser J, Laupitz R, Grawert T, Amslinger S, Eisenreich W, Bacher A, Arigoni D (2003). "The deoxyxylulose phosphate pathway of isoprenoid biosynthesis: studies on the mechanisms of the reactions catalyzed by IspG and IspH protein." Proc Natl Acad Sci U S A 100(4);1586-91. PMID: 12571359

Sharma10: Sharma NK, Pan JJ, Poulter CD (2010). "Type II isopentenyl diphosphate isomerase: probing the mechanism with alkyne/allene diphosphate substrate analogues." Biochemistry 49(29);6228-33. PMID: 20560533

Sherman89: Sherman MM, Petersen LA, Poulter CD (1989). "Isolation and characterization of isoprene mutants of Escherichia coli." J Bacteriol 171(7);3619-28. PMID: 2661529

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

Wouters03: Wouters J, Oudjama Y, Ghosh S, Stalon V, Droogmans L, Oldfield E (2003). "Structure and mechanism of action of isopentenylpyrophosphate-dimethylallylpyrophosphate isomerase." J Am Chem Soc 125(11);3198-9. PMID: 12630859

Wouters03a: Wouters J, Oudjama Y, Barkley SJ, Tricot C, Stalon V, Droogmans L, Poulter CD (2003). "Catalytic mechanism of Escherichia coli isopentenyl diphosphate isomerase involves Cys-67, Glu-116, and Tyr-104 as suggested by crystal structures of complexes with transition state analogues and irreversible inhibitors." J Biol Chem 278(14);11903-8. PMID: 12540835

Wouters04: Wouters J, Oudjama Y, Stalon V, Droogmans L, Poulter CD (2004). "Crystal structure of the C67A mutant of isopentenyl diphosphate isomerase complexed with a mechanism-based irreversible inhibitor." Proteins 54(2);216-21. PMID: 14696183

Wouters05: Wouters J, Yin F, Song Y, Zhang Y, Oudjama Y, Stalon V, Droogmans L, Morita CT, Oldfield E (2005). "A crystallographic investigation of phosphoantigen binding to isopentenyl pyrophosphate/dimethylallyl pyrophosphate isomerase." J Am Chem Soc 127(2);536-7. PMID: 15643873

Wu05d: Wu Z, Wouters J, Poulter CD (2005). "Isopentenyl diphosphate isomerase. Mechanism-based inhibition by diene analogues of isopentenyl diphosphate and dimethylallyl diphosphate." J Am Chem Soc 127(49);17433-8. PMID: 16332094


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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Mon Nov 24, 2014, BIOCYC13B.