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PDBsum entry 1mb4

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1mb4
Jmol
Contents
Protein chains
369 a.a. *
Ligands
CYS ×2
NDP ×2
Waters ×457
* Residue conservation analysis
PDB id:
1mb4
Name: Oxidoreductase
Title: Crystal structure of aspartate semialdehyde dehydrogenase from vibrio cholerae with NADP and s-methyl-l-cysteine sulfoxide
Structure: Aspartate-semialdehyde dehydrogenase. Chain: a, b. Engineered: yes
Source: Vibrio cholerae. Organism_taxid: 666. Gene: asd. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
Resolution:
1.84Å     R-factor:   0.192     R-free:   0.229
Authors: J.Blanco,R.A.Moore,V.Kabaleeswaran,R.E.Viola
Key ref:
J.Blanco et al. (2003). A structural basis for the mechanism of aspartate-beta-semialdehyde dehydrogenase from Vibrio cholerae. Protein Sci, 12, 27-33. PubMed id: 12493825 DOI: 10.1110/ps.0230803
Date:
02-Aug-02     Release date:   07-Jan-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9KQG2  (DHAS1_VIBCH) -  Aspartate-semialdehyde dehydrogenase 1
Seq:
Struc:
370 a.a.
369 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     'de novo' L-methionine biosynthetic process   10 terms 
  Biochemical function     oxidoreductase activity     7 terms  

 

 
    reference    
 
 
DOI no: 10.1110/ps.0230803 Protein Sci 12:27-33 (2003)
PubMed id: 12493825  
 
 
A structural basis for the mechanism of aspartate-beta-semialdehyde dehydrogenase from Vibrio cholerae.
J.Blanco, R.A.Moore, V.Kabaleeswaran, R.E.Viola.
 
  ABSTRACT  
 
L-Aspartate-beta-semialdehyde dehydrogenase (ASADH) catalyzes the reductive dephosphorylation of beta-aspartyl phosphate to L-aspartate-beta-semialdehyde in the aspartate biosynthetic pathway of plants and micro-organisms. The aspartate pathway produces fully one-quarter of the naturally occurring amino acids, but is not found in humans or other eukaryotic organisms, making ASADH an attractive target for the development of new antibacterial, fungicidal, or herbicidal compounds. We have determined the structure of ASADH from Vibrio cholerae in two states; the apoenzyme and a complex with NADP, and a covalently bound active site inhibitor, S-methyl-L-cysteine sulfoxide. Upon binding the inhibitor undergoes an enzyme-catalyzed reductive demethylation leading to a covalently bound cysteine that is observed in the complex structure. The enzyme is a functional homodimer, with extensive intersubunit contacts and a symmetrical 4-amino acid bridge linking the active site residues in adjacent subunits that could serve as a communication channel. The active site is essentially preformed, with minimal differences in active site conformation in the apoenzyme relative to the ternary inhibitor complex. The conformational changes that do occur result primarily from NADP binding, and are localized to the repositioning of two surface loops located on the rim at opposite sides of the NADP cleft.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Ribbon diagram of V. cholerae ASADH dimer with NADP and SMCS bound. The N-terminal domains are shown in darker blue and orange. The central C-terminal domains are shown in red and light blue. Drawings were rendered with Molscript and Raster3D.
Figure 5.
Figure 5. (A) The active sites in the dimer are interconnected through a -stacking interactions and hydrogen bonds. One active site is in the open conformation and the other is closed as shown by the different Pro192 to NADP distances. NADP is shown as a spacefilling model. (B) Diagram of residues involved in the pathway that is proposed to allow communication between the active sites, with the bound inhibitor SMCS shown in lighter shading.
 
  The above figures are reprinted by permission from the Protein Society: Protein Sci (2003, 12, 27-33) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.
PDB code: 3hsk
19595984 D.V.Camper, and R.E.Viola (2009).
Fully automated protein purification.
  Anal Biochem, 393, 176-181.  
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.  
18323627 R.E.Viola, X.Liu, J.F.Ohren, and C.R.Faehnle (2008).
The structure of a redundant enzyme: a second isoform of aspartate beta-semialdehyde dehydrogenase in Vibrio cholerae.
  Acta Crystallogr D Biol Crystallogr, 64, 321-330.
PDB codes: 2qz9 2r00
  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.  
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
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.