PDBsum entry 1tb4

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Oxidoreductase PDB id
Protein chain
357 a.a. *
Waters ×112
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of aspartate-semialdehyde dehydrogenase fr haemophilus influenzae with a bound periodate
Structure: Aspartate-semialdehyde dehydrogenase. Chain: a. Synonym: asa dehydrogenase, asadh. Engineered: yes
Source: Haemophilus influenzae. Organism_taxid: 727. Gene: asd, hi0646. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
2.15Å     R-factor:   0.230     R-free:   0.288
Authors: R.E.Viola
Key ref:
C.R.Faehnle et al. (2004). Structural basis for discrimination between oxyanion substrates or inhibitors in aspartate-beta-semialdehyde dehydrogenase. Acta Crystallogr D Biol Crystallogr, 60, 2320-2324. PubMed id: 15583380 DOI: 10.1107/S0907444904026411
19-May-04     Release date:   07-Dec-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P44801  (DHAS_HAEIN) -  Aspartate-semialdehyde dehydrogenase
371 a.a.
357 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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

Lysine biosynthesis (early stages)
      Reaction: L-aspartate 4-semialdehyde + phosphate + NADP+ = L-4-aspartyl phosphate + NADPH
L-aspartate 4-semialdehyde
+ phosphate
+ NADP(+)
= L-4-aspartyl phosphate
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     'de novo' L-methionine biosynthetic process   10 terms 
  Biochemical function     oxidoreductase activity     7 terms  


DOI no: 10.1107/S0907444904026411 Acta Crystallogr D Biol Crystallogr 60:2320-2324 (2004)
PubMed id: 15583380  
Structural basis for discrimination between oxyanion substrates or inhibitors in aspartate-beta-semialdehyde dehydrogenase.
C.R.Faehnle, J.Blanco, R.E.Viola.
The reversible dephosphorylation of beta-aspartyl phosphate to L-aspartate-beta-semialdehyde (ASA) in the aspartate biosynthetic pathway is catalyzed by aspartate-beta-semialdehyde dehydrogenase (ASADH). The phosphate that is present to activate the aspartate carboxyl group is held in a separate and distinct binding site once removed and prior to its release from the enzyme. This site had been shown to be selective for tetrahedral oxyanions, with several competitive inhibitors and alternative substrates previously identified for the reverse reaction. Structural studies have now shown that the most potent oxyanion inhibitor (periodate) and a good alternative substrate (arsenate) each occupy the same catalytic phosphate-binding site. However, a rotation of a threonine side chain (Thr137) in the periodate complex disrupts an important hydrogen-bonding interaction with an active-site glutamate (Glu243) that participates in substrate orientation. This subtle change appears to be the difference between a substrate and an inhibitor of this enzyme.
  Selected figure(s)  
Figure 1.
Figure 1 An abbreviated mechanism of the reaction catalyzed by aspartate -semialdehyde dehydrogenase in the reverse (non-physiological) direction.
Figure 4.
Figure 4 Stereoview of an overlay of H. influenzae ASA-phosphate structure (blue) and the periodate-bound structure (green). Periodate binding at only the catalytic site results in a reorientation of Thr137 that disrupts the hydrogen bond to an important substrate-orienting group (Glu243). Ser139 is repositioned in the periodate structure and forms a new hydrogen-bonding interaction with the backbone carbonyl of the active-site nucleophile (Cys136).
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2004, 60, 2320-2324) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23034649 M.Elias, A.Wellner, K.Goldin-Azulay, E.Chabriere, J.A.Vorholt, T.J.Erb, and D.S.Tawfik (2012).
The molecular basis of phosphate discrimination in arsenate-rich environments.
  Nature, 491, 134-137.
PDB codes: 4f18 4f19 4f1u 4f1v
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
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