1GZ3

Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.194 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Molecular Mechanism for the Regulation of Human Mitochondrial Nad(P)+-Dependent Malic Enzyme by ATP and Fumarate

Yang, Z.Lanks, C.W.Tong, L.

(2002) Structure 10: 951-960

  • DOI: https://doi.org/10.1016/s0969-2126(02)00788-8
  • Primary Citation of Related Structures:  
    1GZ3, 1GZ4

  • PubMed Abstract: 

    The regulation of human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD-ME) by ATP and fumarate may be crucial for the metabolism of glutamine for energy production in rapidly proliferating tissues and tumors. Here we report the crystal structure at 2.2 A resolution of m-NAD-ME in complex with ATP, Mn2+, tartronate, and fumarate. Our structural, kinetic, and mutagenesis studies reveal unexpectedly that ATP is an active-site inhibitor of the enzyme, despite the presence of an exo binding site. The structure also reveals the allosteric binding site for fumarate in the dimer interface. Mutations in this binding site abolished the activating effects of fumarate. Comparison to the structure in the absence of fumarate indicates a possible molecular mechanism for the allosteric function of this compound.


  • Organizational Affiliation

    Department of Biological Sciences, Columbia University, New York, New York 10027, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NAD-dependent malic enzyme, mitochondrial
A, B, C, D
554Homo sapiensMutation(s): 2 
Gene Names: ME2
EC: 1.1.1.38
UniProt & NIH Common Fund Data Resources
Find proteins for P23368 (Homo sapiens)
Explore P23368 
Go to UniProtKB:  P23368
PHAROS:  P23368
GTEx:  ENSG00000082212 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP23368
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ATP
Query on ATP

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B],
M [auth C],
Q [auth D]
ADENOSINE-5'-TRIPHOSPHATE
C10 H16 N5 O13 P3
ZKHQWZAMYRWXGA-KQYNXXCUSA-N
FUM
Query on FUM

Download Ideal Coordinates CCD File 
H [auth A],
L [auth B],
P [auth C],
T [auth D]
FUMARIC ACID
C4 H4 O4
VZCYOOQTPOCHFL-OWOJBTEDSA-N
OXL
Query on OXL

Download Ideal Coordinates CCD File 
F [auth A],
J [auth B],
N [auth C],
R [auth D]
OXALATE ION
C2 O4
MUBZPKHOEPUJKR-UHFFFAOYSA-L
MN
Query on MN

Download Ideal Coordinates CCD File 
G [auth A],
K [auth B],
O [auth C],
S [auth D]
MANGANESE (II) ION
Mn
WAEMQWOKJMHJLA-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
ATP PDBBind:  1GZ3 Ki: 2.00e+5 (nM) from 1 assay(s)
Binding MOAD:  1GZ3 Ki: 2.00e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.194 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.815α = 90
b = 192.653β = 89.77
c = 110.161γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
COMOphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-05-22
    Type: Initial release
  • Version 1.1: 2011-11-23
    Changes: Database references, Derived calculations, Non-polymer description, Other, Refinement description, Structure summary, Version format compliance
  • Version 1.2: 2018-09-19
    Changes: Data collection, Database references, Source and taxonomy, Structure summary
  • Version 2.0: 2023-11-15
    Changes: Atomic model, Data collection, Database references, Derived calculations