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PDBsum entry 1qr6

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1qr6
Jmol
Contents
Protein chain
551 a.a. *
Ligands
NAD ×4
Waters ×760
* Residue conservation analysis
PDB id:
1qr6
Name: Oxidoreductase
Title: Human mitochondrial NAD(p)-dependent malic enzyme
Structure: Malic enzyme 2. Chain: a, b. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Tetramer (from PDB file)
Resolution:
2.10Å     R-factor:   0.228     R-free:   0.287
Authors: Y.Xu,G.Bhargava,H.Wu,G.Loeber,L.Tong
Key ref: Y.Xu et al. (1999). Crystal structure of human mitochondrial NAD(P)(+)-dependent malic enzyme: a new class of oxidative decarboxylases. Structure, 7, 877-889. PubMed id: 10467136
Date:
18-Jun-99     Release date:   05-Jul-99    
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.
551 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
+
NAD(+)
Bound ligand (Het Group name = NAD)
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    
 
 
Structure 7:877-889 (1999)
PubMed id: 10467136  
 
 
Crystal structure of human mitochondrial NAD(P)(+)-dependent malic enzyme: a new class of oxidative decarboxylases.
Y.Xu, G.Bhargava, H.Wu, G.Loeber, L.Tong.
 
  ABSTRACT  
 
Background: Malic enzymes catalyze the oxidative decarboxylation of malate to pyruvate and CO(2) with the concomitant reduction of NAD(P)(+) to NAD(P)H. They are widely distributed in nature and have important biological functions. Human mitochondrial NAD(P)(+)-dependent malic enzyme (mNAD-ME) may have a crucial role in the metabolism of glutamine for energy production in rapidly dividing cells and tumors. Moreover, this isoform is unique among malic enzymes in that it is a cooperative enzyme, and its activity is controlled allosterically. Results: The crystal structure of human mNAD-ME has been determined at 2.5 Å resolution by the selenomethionyl multiwavelength anomalous diffraction method and refined to 2.1 Å resolution. The structure of the monomer can be divided into four domains; the active site of the enzyme is located in a deep cleft at the interface between three of the domains. Three acidic residues (Glu255, Asp256 and Asp279) were identified as ligands for the divalent cation that is required for catalysis by malic enzymes. Conclusions: The structure reveals that malic enzymes belong to a new class of oxidative decarboxylases. The tetramer of the enzyme appears to be a dimer of dimers. The active site of each monomer is located far from the tetramer interface. The structure also shows the binding of a second NAD(+) molecule in a pocket 35 Å away from the active site. The natural ligand for this second binding site may be ATP, an allosteric inhibitor of the enzyme.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19091740 J.Y.Hsieh, and H.C.Hung (2009).
Engineering of the Cofactor Specificities and Isoform-specific Inhibition of Malic Enzyme.
  J Biol Chem, 284, 4536-4544.  
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.  
20111689 V.Doubnerová, K.Müller, N.Cerovská, H.Synková, P.Spoustová, and H.Ryslavá (2009).
Effect of Potato Virus Y on the NADP-Malic Enzyme from Nicotiana tabacum L.: mRNA, Expressed Protein and Activity.
  Int J Mol Sci, 10, 3583-3598.  
17150960 E.Detarsio, C.E.Alvarez, M.Saigo, C.S.Andreo, and M.F.Drincovich (2007).
Identification of domains involved in tetramerization and malate inhibition of maize C4-NADP-malic enzyme.
  J Biol Chem, 282, 6053-6060.  
17557829 F.P.Bologna, C.S.Andreo, and M.F.Drincovich (2007).
Escherichia coli malic enzymes: two isoforms with substantial differences in kinetic properties, metabolic regulation, and structure.
  J Bacteriol, 189, 5937-5946.  
17704184 H.C.Chang, L.Y.Chen, Y.H.Lu, M.Y.Li, Y.H.Chen, C.H.Lin, and G.G.Chang (2007).
Metal ions stabilize a dimeric molten globule state between the open and closed forms of malic enzyme.
  Biophys J, 93, 3977-3988.  
16757477 J.Y.Hsieh, G.Y.Liu, G.G.Chang, and H.C.Hung (2006).
Determinants of the dual cofactor specificity and substrate cooperativity of the human mitochondrial NAD(P)+-dependent malic enzyme: functional roles of glutamine 362.
  J Biol Chem, 281, 23237-23245.  
15735334 A.Janner (2005).
Strongly correlated structure of axial-symmetric proteins. I. Orthorhombic, tetragonal, trigonal and hexagonal symmetries.
  Acta Crystallogr D Biol Crystallogr, 61, 247-255.  
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.  
12562758 E.Detarsio, M.C.Wheeler, V.A.Campos Bermúdez, C.S.Andreo, and M.F.Drincovich (2003).
Maize C4 NADP-malic enzyme. Expression in Escherichia coli and characterization of site-directed mutants at the putative nucleoside-binding sites.
  J Biol Chem, 278, 13757-13764.  
14596586 G.G.Chang, and L.Tong (2003).
Structure and function of malic enzymes, a new class of oxidative decarboxylases.
  Biochemistry, 42, 12721-12733.  
12853453 G.S.Rao, D.E.Coleman, W.E.Karsten, P.F.Cook, and B.G.Harris (2003).
Crystallographic studies on Ascaris suum NAD-malic enzyme bound to reduced cofactor and identification of an effector site.
  J Biol Chem, 278, 38051-38058.
PDB code: 1o0s
12711612 H.C.Chang, and G.G.Chang (2003).
Involvement of single residue tryptophan 548 in the quaternary structural stability of pigeon cytosolic malic enzyme.
  J Biol Chem, 278, 23996-24002.  
11739398 H.C.Chang, W.Y.Chou, and G.G.Chang (2002).
Effect of metal binding on the structural stability of pigeon liver malic enzyme.
  J Biol Chem, 277, 4663-4671.  
11790843 Z.Yang, H.Zhang, H.C.Hung, C.C.Kuo, L.C.Tsai, H.S.Yuan, W.Y.Chou, G.G.Chang, and L.Tong (2002).
Structural studies of the pigeon cytosolic NADP(+)-dependent malic enzyme.
  Protein Sci, 11, 332-341.
PDB code: 1gq2
11567149 L.Tong (2001).
How to take advantage of non-crystallographic symmetry in molecular replacement: 'locked' rotation and translation functions.
  Acta Crystallogr D Biol Crystallogr, 57, 1383-1389.  
  10716176 W.Y.Chou, H.P.Chang, C.H.Huang, C.C.Kuo, L.Tong, and G.G.Chang (2000).
Characterization of the functional role of Asp141, Asp194, and Asp464 residues in the Mn2+-L-malate binding of pigeon liver malic enzyme.
  Protein Sci, 9, 242-251.  
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.