spacer
spacer

PDBsum entry 3l90

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Transferase PDB id
3l90
Jmol
Contents
Protein chains
370 a.a. *
Ligands
LYS ×2
Metals
_NA ×2
_ZN ×2
Waters ×284
* Residue conservation analysis
Superseded by: 3mi3
PDB id:
3l90
Name: Transferase
Title: Homocitrate synthase lys4 bound to lysine
Structure: Homocitrate synthase, mitochondrial. Chain: a, b. Engineered: yes
Source: Schizosaccharomyces pombe. Fission yeast. Organism_taxid: 4896. Gene: lys4, spbc1105.02c. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
2.38Å     R-factor:   0.172     R-free:   0.204
Authors: S.L.Bulfer,E.M.Scott,L.Pillus,R.C.Trievel
Key ref: S.L.Bulfer et al. (2010). Structural basis for L-lysine feedback inhibition of homocitrate synthase. J Biol Chem, 285, 10446-10453. PubMed id: 20089861 DOI: 10.1074/jbc.M109.094383
Date:
04-Jan-10     Release date:   19-Jan-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9Y823  (HOSM_SCHPO) -  Homocitrate synthase, mitochondrial
Seq:
Struc:
418 a.a.
370 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.3.3.14  - Homocitrate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Oxo-acid lyases with thioester hydrolysis
      Reaction: Acetyl-CoA + H2O + 2-oxoglutarate = (R)-2-hydroxybutane-1,2,4- tricarboxylate + CoA
Acetyl-CoA
+ H(2)O
+ 2-oxoglutarate
= (R)-2-hydroxybutane-1,2,4- tricarboxylate
+ CoA
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M109.094383 J Biol Chem 285:10446-10453 (2010)
PubMed id: 20089861  
 
 
Structural basis for L-lysine feedback inhibition of homocitrate synthase.
S.L.Bulfer, E.M.Scott, L.Pillus, R.C.Trievel.
 
  ABSTRACT  
 
The alpha-aminoadipate pathway of lysine biosynthesis is modulated at the transcriptional and biochemical levels by feedback inhibition. The first enzyme in the alpha-aminoadipate pathway, homocitrate synthase (HCS), is the target of the feedback regulation and is strongly inhibited by l-lysine. Here we report the structure of Schizosaccharomyces pombe HCS (SpHCS) in complex with l-lysine. The structure illustrates that the amino acid directly competes with the substrate 2-oxoglutarate for binding within the active site of HCS. Differential recognition of the substrate and inhibitor is achieved via a switch position within the (alpha/beta)(8) TIM barrel of the enzyme that can distinguish between the C5-carboxylate group of 2-oxoglutarate and the epsilon-ammonium group of l-lysine. In vitro and in vivo assays demonstrate that mutations of the switch residues, which interact with the l-lysine epsilon-ammonium group, abrogate feedback inhibition, as do substitutions of residues within the C-terminal domain that were identified in a previous study of l-lysine-insensitive HCS mutants in Saccharomyces cerevisiae. Together, these results yield new insights into the mechanism of feedback regulation of an enzyme central to lysine biosynthesis.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20810648 E.M.Scott, and L.Pillus (2010).
Homocitrate synthase connects amino acid metabolism to chromatin functions through Esa1 and DNA damage.
  Genes Dev, 24, 1903-1913.  
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.