Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
twitter

Escherichia coli K-12 substr. MG1655 Enzyme: molybdopterin biosynthesis protein A



Gene: moaA Accession Numbers: EG11595 (EcoCyc), b0781, ECK0770

Synonyms: bisA, chlA, chlA1, narA

Regulation Summary Diagram: ?

Summary:
Molybdenum and tungsten cofactors of all enzymes, with the exception of nitrogenase, that require one or the other of the other for activity are present in an oxidized state as molybdate or tungstate ions that are chelated by the cis-dithiolene moiety of a molybdenum cofactor. The particular cofactor that occurs in Escherichia coli is molybdopterin guanine dinucleotide.

This and other molybdenum cofactors are so extremely unstable that they have not been isolated in pure form, and only the outline of their pathway of biosynthesis has been elucidated: a modified guanosine in several steps is converted to a sulfur-free pterin called precursor Z; then by a subsequent series of reactions two sulfhydryl groups are added yielding molybdopterin with its cis-dithiolene moiety; finally molybdenum is inserted to become chelated by the cis-dithiolene moiety and a guanyl group is added yielding molybdopterin guanine dinucleotide the active molybdenum cofactor of E. coli.

Enzymes encoded by the moaABCDE, mobAB, mogA, and moeAB all participate in the synthesis of molybdopterin guanine dinucleotide. A mutational block in any of these proteins leads to a loss of function of all molybdenum enzymes.

Proteins encoded by the moaABCD operon participate in the first two segments of the biosynthetic pathway; the conversion of a guanosine derivative to precursor Z and its conversion to molybdopterin.

Together, MoaA, MoaB and MoaC convert a guanosine derivative to precursor Z [Rieder98].

moaA shows differential codon adaptation, resulting in differential translation efficiency signatures, in thermophilic microbes. It was therefore predicted to play a role in the heat shock response. A moaA deletion mutant was shown to be more sensitive than wild-type specifically to heat shock, but not other stresses [Krisko14].

Citations: [Burgis03]

Gene Citations: [McNicholas97, Rivers93]

Locations: cytosol

Map Position: [816,267 -> 817,256] (17.59 centisomes)
Length: 990 bp / 329 aa

Molecular Weight of Polypeptide: 37.346 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0002669 , CGSC:922 , DIP:DIP-10228N , EchoBASE:EB1552 , EcoGene:EG11595 , EcoliWiki:b0781 , Mint:MINT-1229909 , ModBase:P30745 , OU-Microarray:b0781 , PortEco:moaA , PR:PRO_000023260 , Pride:P30745 , Protein Model Portal:P30745 , RefSeq:NP_415302 , RegulonDB:EG11595 , SMR:P30745 , String:511145.b0781 , UniProt:P30745

Relationship Links: InterPro:IN-FAMILY:IPR000385 , InterPro:IN-FAMILY:IPR006638 , InterPro:IN-FAMILY:IPR007197 , InterPro:IN-FAMILY:IPR010505 , InterPro:IN-FAMILY:IPR013483 , InterPro:IN-FAMILY:IPR013785 , Pfam:IN-FAMILY:PF04055 , Pfam:IN-FAMILY:PF06463 , Prosite:IN-FAMILY:PS01305 , Smart:IN-FAMILY:SM00729

In Paralogous Gene Group: 195 (3 members)

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0009408 - response to heat Inferred from experiment [Krisko14]
GO:0006777 - Mo-molybdopterin cofactor biosynthetic process Inferred by computational analysis [UniProtGOA11a, GOA06, GOA01a]
Molecular Function: GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11a]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01a]
GO:0005525 - GTP binding Inferred by computational analysis [UniProtGOA11a]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0051536 - iron-sulfur cluster binding Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0051539 - 4 iron, 4 sulfur cluster binding Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0061597 - cyclic pyranopterin monophosphate synthase activity Inferred by computational analysis [GOA01]
Cellular Component: GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]
GO:0019008 - molybdopterin synthase complex Inferred by computational analysis [GOA01a]

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

Essentiality data for moaA 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]

Enzymatic reaction of: cyclic pyranopterin monophosphate synthase (molybdopterin biosynthesis protein A)

EC Number: 4.1.99.18

GTP <=> cyclic pyranopterin phosphate + diphosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: molybdenum cofactor biosynthesis

Credits:
Imported from MetaCyc 13-Sep-2011 by Caspi R , SRI International


Sequence Features

Feature Class Location Citations Comment
Amino-Acid-Sites-That-Bind 17
[UniProt10]
UniProt: GTP; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 24
[UniProt10]
UniProt: Iron-sulfur 1 (4Fe-4S-S-AdoMet); Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 28
[UniProt10]
UniProt: Iron-sulfur 1 (4Fe-4S-S-AdoMet); Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 30
[UniProt10]
UniProt: S-adenosyl-L-methionine; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 31
[UniProt10]
UniProt: Iron-sulfur 1 (4Fe-4S-S-AdoMet); Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 68
[UniProt10]
UniProt: GTP; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 72
[UniProt10]
UniProt: S-adenosyl-L-methionine; via carbonyl oxygen; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 99
[UniProt10]
UniProt: GTP; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 123
[UniProt10]
UniProt: S-adenosyl-L-methionine; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 160
[UniProt10]
UniProt: GTP; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 194
[UniProt10]
UniProt: S-adenosyl-L-methionine; via amide nitrogen and carbonyl oxygen; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 257
[UniProt10]
UniProt: Iron-sulfur 2 (4Fe-4S-substrate); Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 260
[UniProt10]
UniProt: Iron-sulfur 2 (4Fe-4S-substrate); Non-Experimental Qualifier: by similarity;
Protein-Segment 262 -> 264
[UniProt10]
UniProt: GTP binding; Sequence Annotation Type: region of interest; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 274
[UniProt10]
UniProt: Iron-sulfur 2 (4Fe-4S-substrate); Non-Experimental Qualifier: by similarity;


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
10/20/97 Gene b0781 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11595; confirmed by SwissProt match.


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

Burgis03: Burgis NE, Brucker JJ, Cunningham RP (2003). "Repair system for noncanonical purines in Escherichia coli." J Bacteriol 185(10);3101-10. PMID: 12730170

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

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

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

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

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

Krisko14: Krisko A, Copi T, Gabaldon T, Lehner B, Supek F (2014). "Inferring gene function from evolutionary change in signatures of translation efficiency." Genome Biol 15(3);R44. PMID: 24580753

McNicholas97: McNicholas PM, Rech SA, Gunsalus RP (1997). "Characterization of the ModE DNA-binding sites in the control regions of modABCD and moaABCDE of Escherichia coli." Mol Microbiol 1997;23(3);515-24. PMID: 9044285

Rieder98: Rieder C, Eisenreich W, O'Brien J, Richter G, Gotze E, Boyle P, Blanchard S, Bacher A, Simon H (1998). "Rearrangement reactions in the biosynthesis of molybdopterin--an NMR study with multiply 13C/15N labelled precursors." Eur J Biochem 255(1);24-36. PMID: 9692897

Rivers93: Rivers SL, McNairn E, Blasco F, Giordano G, Boxer DH (1993). "Molecular genetic analysis of the moa operon of Escherichia coli K-12 required for molybdenum cofactor biosynthesis." Mol Microbiol 1993;8(6);1071-81. PMID: 8361352

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

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

Other References Related to Gene Regulation

Anderson00a: Anderson LA, McNairn E, Lubke T, Pau RN, Boxer DH, Leubke T (2000). "ModE-dependent molybdate regulation of the molybdenum cofactor operon moa in Escherichia coli." J Bacteriol 2000;182(24);7035-43. PMID: 11092866

Regulski08: Regulski EE, Moy RH, Weinberg Z, Barrick JE, Yao Z, Ruzzo WL, Breaker RR (2008). "A widespread riboswitch candidate that controls bacterial genes involved in molybdenum cofactor and tungsten cofactor metabolism." Mol Microbiol 68(4);918-32. PMID: 18363797

Yamamoto05a: Yamamoto K, Ishihama A (2005). "Transcriptional response of Escherichia coli to external copper." Mol Microbiol 56(1);215-27. PMID: 15773991


Report Errors or Provide Feedback
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 Sat Dec 20, 2014, BIOCYC14B.