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Oxidoreductase PDB id
1gl3
Jmol
Contents
Protein chains
367 a.a. *
Ligands
CYS
NDP ×2
Waters ×171
* Residue conservation analysis
PDB id:
1gl3
Name: Oxidoreductase
Title: Aspartate beta-semialdehyde dehydrogenase in complex with NADP and substrate analogue s-methyl cysteine sulfoxide
Structure: Aspartate-semialdehyde dehydrogenase. Chain: a, b. Synonym: asa dehydrogenase, asadh. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Cell_line: jm109. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_cell_line: jm109.
Biol. unit: Dimer (from PDB file)
Resolution:
2.60Å     R-factor:   0.200     R-free:   0.262
Authors: A.T.Hadfield,G.Kryger,J.Ouyang,D.Ringe,G.A.Petsko,R.E.Viola
Key ref:
A.Hadfield et al. (2001). Active site analysis of the potential antimicrobial target aspartate semialdehyde dehydrogenase. Biochemistry, 40, 14475-14483. PubMed id: 11724560 DOI: 10.1021/bi015713o
Date:
23-Aug-01     Release date:   01-Nov-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0A9R0  (DHAS_ECO57) -  Aspartate-semialdehyde dehydrogenase
Seq:
Struc: 		367 a.a.
367 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.2.1.11  - Aspartate-semialdehyde dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Lysine biosynthesis (early stages)
      Reaction: L-aspartate 4-semialdehyde + phosphate + NADP+ = L-4-aspartyl phosphate + NADPH
L-aspartate 4-semialdehyde
Bound ligand (Het Group name = CYS)
matches with 66.00% similarity 		+ phosphate
 +
NADP(+)
Bound ligand (Het Group name = NDP)
corresponds exactly 		= L-4-aspartyl phosphate
 + NADPH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     oxidation-reduction process   9 terms 
  Biochemical function     nucleotide binding     8 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi015713o Biochemistry 40:14475-14483 (2001)
PubMed id: 11724560  
 
 
Active site analysis of the potential antimicrobial target aspartate semialdehyde dehydrogenase.
A.Hadfield, C.Shammas, G.Kryger, D.Ringe, G.A.Petsko, J.Ouyang, R.E.Viola.
 
  ABSTRACT  
 
Aspartate-beta-semialdehyde dehydrogenase (ASADH) lies at the first branch point in the biosynthetic pathway through which bacteria, fungi, and the higher plants synthesize amino acids, including lysine and methionine and the cell wall component diaminopimelate from aspartate. Blocks in this biosynthetic pathway, which is absent in mammals, are lethal, and inhibitors of ASADH may therefore serve as useful antibacterial, fungicidal, or herbicidal agents. We have determined the structure of ASADH from Escherichia coli by crystallography in the presence of its coenzyme and a substrate analogue that acts as a covalent inhibitor. This structure is comparable to that of the covalent intermediate that forms during the reaction catalyzed by ASADH. The key catalytic residues are confirmed as cysteine 135, which is covalently linked to the intermediate during the reaction, and histidine 274, which acts as an acid/base catalyst. The substrate and coenzyme binding residues are also identified, and these active site residues are conserved throughout all of the ASADH sequences. Comparison of the previously determined apo-enzyme structure [Hadfield et al. J. Mol. Biol. and the complex presented here reveals a conformational change that occurs on binding of NADP that creates a binding site for the amino acid substrate. These results provide a structural explanation for the preferred order of substrate binding that is observed kinetically.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21369577 A.S.Evitt, and R.J.Cox (2011).
Synthesis and evaluation of conformationally restricted inhibitors of aspartate semialdehyde dehydrogenase.
  Mol Biosyst, 7, 1564-1575.  
20124701 B.T.Arachea, X.Liu, A.G.Pavlovsky, and R.E.Viola (2010).
Expansion of the aspartate beta-semialdehyde dehydrogenase family: the first structure of a fungal ortholog.
  Acta Crystallogr D Biol Crystallogr, 66, 205-212.  
18236087 A.Singh, H.R.Kushwaha, and P.Sharma (2008).
Molecular modelling and comparative structural account of aspartyl beta-semialdehyde dehydrogenase of Mycobacterium tuberculosis (H37Rv).
  J Mol Model, 14, 249-263.  
  18323599 R.Vyas, V.Kumar, S.Panjikar, S.Karthikeyan, K.V.Kishan, R.Tewari, and M.S.Weiss (2008).
Purification, crystallization and preliminary X-ray diffraction analysis of aspartate semialdehyde dehydrogenase (Rv3708c) from Mycobacterium tuberculosis.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 167-170.  
16895909 C.R.Faehnle, J.Le Coq, X.Liu, and R.E.Viola (2006).
Examination of key intermediates in the catalytic cycle of aspartate-beta-semialdehyde dehydrogenase from a gram-positive infectious bacteria.
  J Biol Chem, 281, 31031-31040.
PDB codes: 2gyy 2gz1 2gz2 2gz3
16525757 R.A.Azevedo, M.Lancien, and P.J.Lea (2006).
The aspartic acid metabolic pathway, an exciting and essential pathway in plants.
  Amino Acids, 30, 143-162.  
16261551 R.J.Cox, J.S.Gibson, and A.T.Hadfield (2005).
Design, synthesis and analysis of inhibitors of bacterial aspartate semialdehyde dehydrogenase.
  Chembiochem, 6, 2255-2260.  
16240442 T.Nonaka, A.Kita, J.Miura-Ohnuma, E.Katoh, N.Inagaki, T.Yamazaki, and K.Miki (2005).
Crystal structure of putative N-acetyl-gamma-glutamyl-phosphate reductase (AK071544) from rice (Oryza sativa).
  Proteins, 61, 1137-1140.
PDB code: 2cvo
15583380 C.R.Faehnle, J.Blanco, and R.E.Viola (2004).
Structural basis for discrimination between oxyanion substrates or inhibitors in aspartate-beta-semialdehyde dehydrogenase.
  Acta Crystallogr D Biol Crystallogr, 60, 2320-2324.
PDB codes: 1ta4 1tb4
15272161 J.Blanco, R.A.Moore, C.R.Faehnle, D.M.Coe, and R.E.Viola (2004).
The role of substrate-binding groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase.
  Acta Crystallogr D Biol Crystallogr, 60, 1388-1395.
PDB codes: 1oza 1pqp 1pqu 1pr3 1ps8 1pu2 1q2x
15388927 J.Blanco, R.A.Moore, C.R.Faehnle, and R.E.Viola (2004).
Critical catalytic functional groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase.
  Acta Crystallogr D Biol Crystallogr, 60, 1808-1815.  
14559965 J.Blanco, R.A.Moore, and R.E.Viola (2003).
Capture of an intermediate in the catalytic cycle of L-aspartate-beta-semialdehyde dehydrogenase.
  Proc Natl Acad Sci U S A, 100, 12613-12617.
PDB codes: 1nwc 1nwh 1nx6
12493825 J.Blanco, R.A.Moore, V.Kabaleeswaran, and R.E.Viola (2003).
A structural basis for the mechanism of aspartate-beta-semialdehyde dehydrogenase from Vibrio cholerae.
  Protein Sci, 12, 27-33.
PDB codes: 1mb4 1mc4
12496312 Z.Yang, A.Savchenko, A.Yakunin, R.Zhang, A.Edwards, C.Arrowsmith, and L.Tong (2003).
Aspartate dehydrogenase, a novel enzyme identified from structural and functional studies of TM1643.
  J Biol Chem, 278, 8804-8808.
PDB code: 1h2h
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 codes are shown on the right.