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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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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.
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MetaCyc Enzyme: D-malate / 3-isopropylmalate dehydrogenase (decarboxylating)

Gene: dmlA Accession Numbers: G6986 (MetaCyc), b1800, ECK1798

Synonyms: ttuC, yeaU

Species: Escherichia coli K-12 substr. MG1655

Summary:
DmlA is a D-malate dehydrogenase that is essential for aerobic growth on D-malate as the sole carbon source [Reed06, Lukas10]. DmlA also catalyses the oxidative decarboxylation of 3-isopropylmalate in vitro and in vivo and the non-decarboxylating oxidation of L(+)-tartrate in vitro. DmlA is a generalist enzyme and displays relatively high activity on 3 differing substrates [Vorobieva14].

Expression of dmlA is increased more than 500-fold during growth on D-malate compared to growth on L-lactate [Reed06], L-malate, glucose or glycerol [Stern66]. Under anaerobic conditions, expression of dmlA is increased even further by the presence of D-malate; however, anaerobic growth on D-malate requires the presence of an additional electron donor such as glycerol [Lukas10].

Chromosomal expression of dmlA is able to complement cells lacking leuB encoded 3-isopropylmalate dehydrogenase (IPMDH) activity. Purified DmlA is active on D-malate, 3-isopropylmalate and L(+)-tartrate; D-lactate, isocitrate and D-tartrate are poor substrates. DmlA has a weaker affinity for L(+)-tartrate than for D-malate or 3-isopropylmalate [Vorobieva14].

Protein levels of DmlA are upregulated in response to Zn(II) stress (growth in 0.2 mM Zn(II) for 4 hours) [Easton06].

DmlA: "D-malate degradation A" [Lukas10]

Locations: cytosol

Map Position: [1,879,936 -> 1,881,021]

Molecular Weight of Polypeptide: 40.315 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0005991 , DIP:DIP-11800N , EchoBASE:EB3280 , EcoGene:EG13507 , EcoliWiki:b1800 , Mint:MINT-1273575 , ModBase:P76251 , OU-Microarray:b1800 , PortEco:yeaU , Pride:P76251 , Protein Model Portal:P76251 , RefSeq:NP_416314 , RegulonDB:G6986 , SMR:P76251 , String:511145.b1800 , UniProt:P76251

Relationship Links: InterPro:IN-FAMILY:IPR001804 , InterPro:IN-FAMILY:IPR011829 , InterPro:IN-FAMILY:IPR019818 , InterPro:IN-FAMILY:IPR024084 , Panther:IN-FAMILY:PTHR11835 , Pfam:IN-FAMILY:PF00180 , Prosite:IN-FAMILY:PS00470

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0006108 - malate metabolic process Inferred from experiment [Lukas10, Reed06]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11, GOA01]
Molecular Function: GO:0000287 - magnesium ion binding Inferred by computational analysis Inferred from experiment [Vorobieva14, GOA01]
GO:0003862 - 3-isopropylmalate dehydrogenase activity Inferred from experiment [Vorobieva14]
GO:0009027 - tartrate dehydrogenase activity Inferred from experiment [Vorobieva14]
GO:0046553 - D-malate dehydrogenase (decarboxylating) activity Inferred by computational analysis Inferred from experiment [Vorobieva14, GOA01a, Lukas10, Reed06]
GO:0051287 - NAD binding Inferred by computational analysis Inferred from experiment [Vorobieva14, GOA01]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11]
GO:0016616 - oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor Inferred by computational analysis [GOA01]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11a, UniProtGOA11]
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism carbon utilization carbon compounds

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: D-malate dehydrogenase (decarboxylating) (D-malate / 3-isopropylmalate dehydrogenase (decarboxylating))

EC Number: 1.1.1.83

(R)-malate + NAD+ <=> pyruvate + CO2 + NADH

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown. [Stern66]

In Pathways: D-malate degradation

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
Both divalent (Mg2+ or Mn2+) and monovalent (K+, NH4+ or Rb+) cations were required for activity of the enzyme in crude extracts [Stern66]. Activity of the purified enzyme depends on Mg2+ or Mn2+; catalysis is activated by K+ or NH4+ but activity decreases in the presence of Na+. The purified enzyme prefers NAD to NADP [Vorobieva14].

Cofactors or Prosthetic Groups: K+ [Stern66], Mg2+ [Stern66]

Kinetic Parameters:

Substrate
Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)
Citations
(R)-malate
96.0
11.7
[Vorobieva14]
NAD+
94.0
[Vorobieva14]


Enzymatic reaction of: 3-isopropylmalate dehydrogenase (decarboxylating)

(2R,3S)-3-isopropylmalate + NAD+ <=> (2S)-2-isopropyl-3-oxosuccinate + NADH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of leucine, valine, and isoleucine biosynthesis , leucine biosynthesis , 3-methylbutanol biosynthesis

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Kinetic Parameters:

Substrate
Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)
Citations
(2R,3S)-3-isopropylmalate
24.0
0.1
[Vorobieva14]
NAD+
70.0
[Vorobieva14]


Enzymatic reaction of: L-tartrate dehydrogenase (decarboxylating) (D-malate / 3-isopropylmalate dehydrogenase (decarboxylating))

EC Number: 1.1.1.93

L-tartrate + NAD+ <=> 2-hydroxy-3-oxosuccinate + NADH + H+

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

This reaction is reversible.

Note: The enzyme may catalyze this reaction in vitro, but this reaction is not considered to be physiologically relevant.

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Kinetic Parameters:

Substrate
Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)
Citations
L-tartrate
567.0
0.26
[Vorobieva14]
NAD+
600.0
[Vorobieva14]


Sequence Features

Feature Class Location Citations Comment
Conserved-Region 88 -> 98
[Vorobieva14]
substrate recognition region

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


References

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

Easton06: Easton JA, Thompson P, Crowder MW (2006). "Time-dependent translational response of E. coli to excess Zn(II)." J Biomol Tech 17(5);303-7. PMID: 17122063

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.

Lukas10: Lukas H, Reimann J, Kim OB, Grimpo J, Unden G (2010). "Regulation of aerobic and anaerobic D-malate metabolism of Escherichia coli by the LysR-type regulator DmlR (YeaT)." J Bacteriol 192(10);2503-11. PMID: 20233924

Reed06: Reed JL, Patel TR, Chen KH, Joyce AR, Applebee MK, Herring CD, Bui OT, Knight EM, Fong SS, Palsson BO (2006). "Systems approach to refining genome annotation." Proc Natl Acad Sci U S A 103(46);17480-4. PMID: 17088549

Stern66: Stern JR, Hegre CS (1966). "Inducible D-Malic Enzyme in Escherichia coli." Nature 212:1611-12.

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."

Vorobieva14: Vorobieva AA, Khan MS, Soumillion P (2014). "Escherichia coli D-Malate Dehydrogenase: a Generalist Enzyme Active in the Leucine Biosynthesis Pathway." J Biol Chem. PMID: 25160617


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sun Dec 21, 2014, biocyc13.