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PDBsum entry 1nzz

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1nzz
Jmol
Contents
Protein chain
(+ 2 more) 494 a.a. *
Ligands
NAI ×8
Metals
_NA ×8
_MG ×8
Waters ×1298
* Residue conservation analysis
PDB id:
1nzz
Name: Oxidoreductase
Title: Human mitochondrial aldehyde dehydrogenase complexed with na presence of low mg2+
Structure: Aldehyde dehydrogenase. Chain: a, b, c, d, e, f, g, h. Fragment: complete mature sequence (does not contain mitoch leader sequence).. Synonym: aldh class 2, aldhi, aldh-e2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: aldh2 or aldm. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Tetramer (from PQS)
Resolution:
2.45Å     R-factor:   0.215     R-free:   0.248
Authors: S.J.Perez-Miller,T.D.Hurley
Key ref:
S.J.Perez-Miller and T.D.Hurley (2003). Coenzyme isomerization is integral to catalysis in aldehyde dehydrogenase. Biochemistry, 42, 7100-7109. PubMed id: 12795606 DOI: 10.1021/bi034182w
Date:
20-Feb-03     Release date:   24-Jun-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P05091  (ALDH2_HUMAN) -  Aldehyde dehydrogenase, mitochondrial
Seq:
Struc:
517 a.a.
494 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.2.1.3  - Aldehyde dehydrogenase (NAD(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An aldehyde + NAD+ + H2O = a carboxylate + NADH
aldehyde
+
NAD(+)
Bound ligand (Het Group name = NAI)
corresponds exactly
+ H(2)O
= carboxylate
+ NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular vesicular exosome   3 terms 
  Biological process     metabolic process   10 terms 
  Biochemical function     electron carrier activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi034182w Biochemistry 42:7100-7109 (2003)
PubMed id: 12795606  
 
 
Coenzyme isomerization is integral to catalysis in aldehyde dehydrogenase.
S.J.Perez-Miller, T.D.Hurley.
 
  ABSTRACT  
 
Crystal structures of many enzymes in the aldehyde dehydrogenase superfamily determined in the presence of bound NAD(P)(+) have exhibited conformational flexibility for the nicotinamide half of the cofactor. This has been hypothesized to be important in catalysis because one conformation would block the second half of the reaction, but no firm evidence has been put forth which shows whether the oxidized and reduced cofactors preferentially occupy the two observed conformations. We present here two structures of the wild type and two structures of a Cys302Ser mutant of human mitochondrial aldehyde dehydrogenase in binary complexes with NAD(+) and NADH. These structures, including the Cys302Ser mutant in complex with NAD(+) at 1.4 A resolution and the wild-type enzyme in complex with NADH at 1.9 A resolution, provide strong evidence that bound NAD(+) prefers an extended conformation ideal for hydride transfer and bound NADH prefers a contracted conformation ideal for acyl-enzyme hydrolysis. Unique interactions between the cofactor and the Rossmann fold make isomerization possible while allowing the remainder of the active site complex to remain intact. In addition, these structures clarify the role of magnesium in activating the human class 2 enzyme. Our data suggest that the presence of magnesium may lead to selection of particular conformations and speed isomerization of the reduced cofactor following hydride transfer.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21303655 L.P.de Carvalho, Y.Ling, C.Shen, J.D.Warren, and K.Y.Rhee (2011).
On the chemical mechanism of succinic semialdehyde dehydrogenase (GabD1) from Mycobacterium tuberculosis.
  Arch Biochem Biophys, 509, 90-99.  
20174634 C.G.Langendorf, T.L.Key, G.Fenalti, W.T.Kan, A.M.Buckle, T.Caradoc-Davies, K.L.Tuck, R.H.Law, and J.C.Whisstock (2010).
The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.
  PLoS One, 5, e9280.
PDB code: 3jz4
20062057 S.Perez-Miller, H.Younus, R.Vanam, C.H.Chen, D.Mochly-Rosen, and T.D.Hurley (2010).
Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant.
  Nat Struct Mol Biol, 17, 159-164.
PDB codes: 3inj 3inl
19911309 C.Y.Kim, C.Webster, J.K.Roberts, J.H.Moon, E.Z.Alipio Lyon, H.Kim, M.Yu, L.W.Hung, and T.C.Terwilliger (2009).
Analysis of nucleoside-binding proteins by ligand-specific elution from dye resin: application to Mycobacterium tuberculosis aldehyde dehydrogenases.
  J Struct Funct Genomics, 10, 291-301.  
19480389 L.Hedstrom (2009).
IMP dehydrogenase: structure, mechanism, and inhibition.
  Chem Rev, 109, 2903-2928.  
19506075 M.V.Wenzl, M.Beretta, A.C.Gorren, A.Zeller, P.K.Baral, K.Gruber, M.Russwurm, D.Koesling, K.Schmidt, and B.Mayer (2009).
Role of the general base Glu-268 in nitroglycerin bioactivation and superoxide formation by aldehyde dehydrogenase-2.
  J Biol Chem, 284, 19878-19886.  
18848533 S.A.Krupenko (2009).
FDH: an aldehyde dehydrogenase fusion enzyme in folate metabolism.
  Chem Biol Interact, 178, 84-93.  
17327228 H.N.Larson, J.Zhou, Z.Chen, J.S.Stamler, H.Weiner, and T.D.Hurley (2007).
Structural and functional consequences of coenzyme binding to the inactive asian variant of mitochondrial aldehyde dehydrogenase: roles of residues 475 and 487.
  J Biol Chem, 282, 12940-12950.
PDB codes: 2onm 2onn 2ono 2onp
17173928 L.Di Costanzo, G.A.Gomez, and D.W.Christianson (2007).
Crystal structure of lactaldehyde dehydrogenase from Escherichia coli and inferences regarding substrate and cofactor specificity.
  J Mol Biol, 366, 481-493.
PDB codes: 2hg2 2ilu 2imp
17655326 T.Wymore, D.W.Deerfield, and J.Hempel (2007).
Mechanistic implications of the cysteine-nicotinamide adduct in aldehyde dehydrogenase based on quantum mechanical/molecular mechanical simulations.
  Biochemistry, 46, 9495-9506.  
16267046 E.Di Cera (2006).
A structural perspective on enzymes activated by monovalent cations.
  J Biol Chem, 281, 1305-1308.  
15983043 H.N.Larson, H.Weiner, and T.D.Hurley (2005).
Disruption of the coenzyme binding site and dimer interface revealed in the crystal structure of mitochondrial aldehyde dehydrogenase "Asian" variant.
  J Biol Chem, 280, 30550-30556.
PDB code: 1zum
15757901 S.Rahuel-Clermont, D.Arutyunov, S.Marchal, V.Orlov, V.Muronetz, and G.Branlant (2005).
Thermal destabilization of non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Streptococcus mutans upon phosphate binding in the active site.
  J Biol Chem, 280, 18590-18597.  
15299009 T.Bordelon, S.K.Montegudo, S.Pakhomova, M.L.Oldham, and M.E.Newcomer (2004).
A disorder to order transition accompanies catalysis in retinaldehyde dehydrogenase type II.
  J Biol Chem, 279, 43085-43091.  
15390260 T.Wymore, J.Hempel, S.S.Cho, A.D.Mackerell, H.B.Nicholas, and D.W.Deerfield (2004).
Molecular recognition of aldehydes by aldehyde dehydrogenase and mechanism of nucleophile activation.
  Proteins, 57, 758-771.  
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.