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Overview for MACiE Entry M0021

Version history

General Information

EC Number: 1.1.1.38 (A member of the Oxidoreductases, Acting on the CH-OH group of donors, With NAD+ or NADP+ as acceptor)

Enzyme Name: malate dehydrogenase (oxaloacetate-decarboxylating)

Biological Species: Homo sapiens (Human)

Catalytic Chain UniprotKB Accession Codes:

  • P23368 - NAD-dependent malic enzyme, mitochondrial

Representative PDB Code: 1do8 - CRYSTAL STRUCTURE OF A CLOSED FORM OF HUMAN MITOCHONDRIALNAD(P)+-DEPENDENT MALIC ENZYME (Resolution = 2.20 Å).

Catalytic CATH Codes:

  • 3.40.50.10380 - Aminoacid dehydrogenase-like, N-terminal domain. Chain A
  • 3.40.50.720 - NAD(P)-binding Rossmann-like Domain

Display structure information

Overall Reaction:

Image of NADP

Image of L-malate

right arrow

Image of NADPH

Image of carbon dioxide

Image of pyruvate

NADP
C00006
CHEBI:18009
L-malate
C00149
CHEBI:15589
NADPH
C00005
CHEBI:16474
carbon dioxide
C00011
CHEBI:16526
pyruvate
C00022
CHEBI:15361

Overall Comment: Fumarate is an allosteric activator, and ATP is an allosteric inhibitor.


View similar reactions


Stepwise Description of the Reaction

Step 1Asp278 deprotonates Lys183, which deprotonates the hydroxyl group of malate, which eliminates a hydride ion that is added to NADP.
Step 2The reduced intermediate decarboxylates with concomitant double bond rearrangement.
Step 3The oxyanion collapses, reducing the C=C with concomitant deprotonation of Tyr112.
Step 4Tyr112 deprotonates Lys183 which deprotonates Asp278 in an inferred return step.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Tyr 112 A Side Chain
Arg 165 A Side Chain
Lys 183 A Side Chain
Asp 278 A Side Chain
Asn 421 A Side Chain

Metal Cofactors for M0021

Type Het group Number Chain
manganese MN 604 x Overview

References

  1. Z. Yang et al. (2000), Nat. Struct. Biol., 7, 251-257. Structure of a closed form of human malic enzyme and implications for catalytic mechanism.
    Medline: 10700286
  2. X. Tao et al. (2003), Structure, 11, 1141-1150. Crystal structures of substrate complexes of malic enzyme and insights into the catalytic mechanism.
    Medline: 12962632

Homologue information for M0021 (1do8)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)



Entries with at least one Catalytic CATH code in common (different mechanisms):

MACiE Entry Enzyme Name
EC Number
PDB code CATH code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0255 alcohol dehydrogenase
1.1.1.1
1mg5 3.40.50.720
0.56750.2999Compare
M0092 UDP-glucose 6-dehydrogenase
1.1.1.22
1dli 3.40.50.720
0.68420.3375Compare
M0227 GDP-L-fucose synthase
1.1.1.271
1e6u 3.40.50.720
0.4690.1741Compare
M0110 D-amino-acid oxidase
1.4.3.3
1c0p 3.40.50.720
0.50.1407Compare
M0237 pteridine reductase
1.5.1.33
2c7v 3.40.50.720
0.60.5484Compare
M0116 NAD(P)+ transhydrogenase (AB-specific)
1.6.1.2
1hzz 3.40.50.720
0.33330.5311Compare
M0142 ferredoxin-NADP+ reductase
1.18.1.2
1e6e 3.40.50.720
0.29260.1233Compare
M0090 adenosylhomocysteinase
3.3.1.1
1b3r 3.40.50.720
0.6610.2868Compare
M0226 UDP-sulfoquinovose synthase
3.13.1.1
1qrr 3.40.50.720
0.59640.236Compare
M0228 dTDP-glucose 4,6-dehydratase
4.2.1.46
1bxk 3.40.50.720
0.50.3856Compare
M0188 UDP-glucose 4-epimerase
5.1.3.2
1xel 3.40.50.720
0.57570.2999Compare

View a comparison of the other reactions in MACiE with the CATH domain 3.40.50.720


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ
Link to EzCatDB

GOA logo
catalytic activity (molecular function)
malic enzyme activity (molecular function)
malate dehydrogenase (decarboxylating) (NAD+) activity (molecular function)
binding (molecular function)
mitochondrion (cellular component)
mitochondrial matrix (cellular component)
malate metabolic process (biological process)
metabolic process (biological process)
electron carrier activity (molecular function)
oxidoreductase activity (molecular function)
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (molecular function)
()
intracellular membrane-bounded organelle (cellular component)
metal ion binding (molecular function)
NAD binding (molecular function)
oxidation-reduction process (biological process)
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