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PDBsum entry 1pj2

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1pj2
Jmol
Contents
Protein chain
553 a.a. *
Ligands
MLT ×4
NAI ×8
FUM ×4
Metals
_MN ×4
Waters ×748
* Residue conservation analysis
PDB id:
1pj2
Name: Oxidoreductase
Title: Crystal structure of human mitochondrial NAD(p)+-dependent malic enzyme in a pentary complex with natural substrate malate, cofactor nadh, mn++, and allosteric activator fumarate
Structure: NAD-dependent malic enzyme, mitochondrial. Chain: a, b, c, d. Synonym: NAD-me, malic enzyme 2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: me2. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Tetramer (from PQS)
Resolution:
2.30Å     R-factor:   0.205     R-free:   0.256
Authors: X.Tao,Z.Yang,L.Tong
Key ref:
X.Tao et al. (2003). Crystal structures of substrate complexes of malic enzyme and insights into the catalytic mechanism. Structure, 11, 1141-1150. PubMed id: 12962632 DOI: 10.1016/S0969-2126(03)00168-0
Date:
30-May-03     Release date:   11-Nov-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P23368  (MAOM_HUMAN) -  NAD-dependent malic enzyme, mitochondrial
Seq:
Struc:
 
Seq:
Struc:
584 a.a.
553 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.38  - Malate dehydrogenase (oxaloacetate-decarboxylating).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. (S)-malate + NAD+ = pyruvate + CO2 + NADH
2. Oxaloacetate = pyruvate + CO2
(S)-malate
Bound ligand (Het Group name = MLT)
corresponds exactly
+
NAD(+)
Bound ligand (Het Group name = NAI)
corresponds exactly
= pyruvate
+ CO(2)
+ NADH
Oxaloacetate
= pyruvate
+ CO(2)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular membrane-bounded organelle   3 terms 
  Biological process     metabolic process   3 terms 
  Biochemical function     catalytic activity     8 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(03)00168-0 Structure 11:1141-1150 (2003)
PubMed id: 12962632  
 
 
Crystal structures of substrate complexes of malic enzyme and insights into the catalytic mechanism.
X.Tao, Z.Yang, L.Tong.
 
  ABSTRACT  
 
Malic enzymes catalyze the oxidative decarboxylation of L-malate to pyruvate and CO(2) with the reduction of the NAD(P)(+) cofactor in the presence of divalent cations. We report the crystal structures at up to 2.1 A resolution of human mitochondrial NAD(P)(+)-dependent malic enzyme in different pentary complexes with the natural substrate malate or pyruvate, the dinucleotide cofactor NAD(+) or NADH, the divalent cation Mn(2+), and the allosteric activator fumarate. Malate is bound deep in the active site, providing two ligands for the cation, and its C4 carboxylate group is out of plane with the C1-C2-C3 atoms, facilitating decarboxylation. The divalent cation is positioned optimally to catalyze the entire reaction. Lys183 is the general base for the oxidation step, extracting the proton from the C2 hydroxyl of malate. Tyr112-Lys183 functions as the general acid-base pair to catalyze the tautomerization of the enolpyruvate product from decarboxylation to pyruvate.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Structure of Human m-NAD-ME in Complex with NADH, L-Malate, Mn2+, and Fumarate(A) Schematic drawing of the monomer of human m-NAD-ME. b strands, cyan; a helices, yellow; connecting loops, purple. The NADH molecule in the active site, the ADP portion of the NADH molecule in the exo site, malate (M), and fumarate are shown as stick models, colored in gray for carbon atoms. The Mn2+ ion and its liganding water are shown as pink and red spheres, respectively.(B) Schematic drawing of the tetramer of the enzyme. The monomers are colored in cyan, green, yellow, and purple, respectively. The fumarate molecules are in the dimer interface (F). This figure was produced with Ribbons (Carson, 1987).
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 1141-1150) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19236308 J.Y.Hsieh, J.H.Liu, Y.W.Fang, and H.C.Hung (2009).
Dual roles of Lys(57) at the dimer interface of human mitochondrial NAD(P)+-dependent malic enzyme.
  Biochem J, 420, 201-209.  
19416979 J.Y.Hsieh, S.H.Chen, and H.C.Hung (2009).
Functional roles of the tetramer organization of malic enzyme.
  J Biol Chem, 284, 18096-18105.  
18959763 J.Y.Hsieh, G.Y.Liu, and H.C.Hung (2008).
Influential factor contributing to the isoform-specific inhibition by ATP of human mitochondrial NAD(P)+-dependent malic enzyme: functional roles of the nucleotide binding site Lys346.
  FEBS J, 275, 5383-5392.  
18288573 M.C.Wheeler, C.L.Arias, M.A.Tronconi, V.G.Maurino, C.S.Andreo, and M.F.Drincovitch (2008).
Arabidopsis thaliana NADP-malic enzyme isoforms: high degree of identity but clearly distinct properties.
  Plant Mol Biol, 67, 231-242.  
18823933 N.E.Voynova, Z.Fu, K.P.Battaile, T.J.Herdendorf, J.J.Kim, and H.M.Miziorko (2008).
Human mevalonate diphosphate decarboxylase: characterization, investigation of the mevalonate diphosphate binding site, and crystal structure.
  Arch Biochem Biophys, 480, 58-67.
PDB code: 3d4j
17962075 R.P.Hirt, C.J.Noel, T.Sicheritz-Ponten, J.Tachezy, and P.L.Fiori (2007).
Trichomonas vaginalis surface proteins: a view from the genome.
  Trends Parasitol, 23, 540-547.  
16963440 M.Goto, H.Hayashi, I.Miyahara, K.Hirotsu, M.Yoshida, and T.Oikawa (2006).
Crystal structures of nonoxidative zinc-dependent 2,6-dihydroxybenzoate (gamma-resorcylate) decarboxylase from Rhizobium sp. strain MTP-10005.
  J Biol Chem, 281, 34365-34373.
PDB codes: 2dvt 2dvu 2dvx
16437252 M.Saayman, W.H.van Zyl, and M.Viljoen-Bloom (2006).
Cloning, characterisation, and heterologous expression of the Candida utilis malic enzyme gene.
  Curr Genet, 49, 248-258.  
16889632 S.C.Chang, K.Y.Lin, Y.J.Chen, C.H.Lai, G.G.Chang, and W.Y.Chou (2006).
Critical roles of conserved carboxylic acid residues in pigeon cytosolic NADP+-dependent malic enzyme.
  FEBS J, 273, 4072-4081.  
14747989 C.W.Kuo, H.C.Hung, L.Tong, and G.G.Chang (2004).
Metal-Induced reversible structural interconversion of human mitochondrial NAD(P)+-dependent malic enzyme.
  Proteins, 54, 404-411.  
14596586 G.G.Chang, and L.Tong (2003).
Structure and function of malic enzymes, a new class of oxidative decarboxylases.
  Biochemistry, 42, 12721-12733.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.