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PDBsum entry 2vxn

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protein ligands links
Isomerase PDB id
2vxn
Jmol
Contents
Protein chain
249 a.a. *
Ligands
PGH
PGA
GOL ×5
ACT
Waters ×419
* Residue conservation analysis
PDB id:
2vxn
Name: Isomerase
Title: E65q-tim complexed with phosphoglycolohydroxamate at 0.82 a resolution
Structure: Triosephosphate isomerase. Chain: a. Synonym: tim, triose-phosphate isomerase. Engineered: yes. Mutation: yes
Source: Leishmania mexicana. Organism_taxid: 5665. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Resolution:
0.82Å     R-factor:   0.092     R-free:   0.103
Authors: M.Alahuhta,R.K.Wierenga
Key ref: M.Alahuhta and R.K.Wierenga (2010). Atomic resolution crystallography of a complex of triosephosphate isomerase with a reaction-intermediate analog: new insight in the proton transfer reaction mechanism. Proteins, 78, 1878-1888. PubMed id: 20235230
Date:
08-Jul-08     Release date:   14-Jul-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P48499  (TPIS_LEIME) -  Triosephosphate isomerase
Seq:
Struc:
251 a.a.
249 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.5.3.1.1  - Triose-phosphate isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: D-glyceraldehyde 3-phosphate = glycerone phosphate
D-glyceraldehyde 3-phosphate
Bound ligand (Het Group name = PGH)
matches with 66.67% similarity
= glycerone phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   3 terms 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     3 terms  

 

 
    Added reference    
 
 
Proteins 78:1878-1888 (2010)
PubMed id: 20235230  
 
 
Atomic resolution crystallography of a complex of triosephosphate isomerase with a reaction-intermediate analog: new insight in the proton transfer reaction mechanism.
M.Alahuhta, R.K.Wierenga.
 
  ABSTRACT  
 
Enzymes achieve their catalytic proficiency by precisely positioning the substrate and catalytic residues with respect to each other. Atomic resolution crystallography is an excellent tool to study the important details of these geometric active-site features. Here, we have investigated the reaction mechanism of triosephosphate isomerase (TIM) using atomic resolution crystallographic studies at 0.82-A resolution of leishmanial TIM complexed with the well-studied reaction-intermediate analog phosphoglycolohydroxamate (PGH). Remaining unresolved aspects of the reaction mechanism of TIM such as the protonation state of the first reaction intermediate and the properties of the hydrogen-bonding interactions in the active site are being addressed. The hydroxamate moiety of PGH interacts via unusually short hydrogen bonds of its N1-O1 moiety with the carboxylate group of the catalytic glutamate (Glu167), for example, the distance of N1(PGH)-OE2(Glu167) is 2.69 +/- 0.01 A and the distance of O1(PGH)-OE1(Glu167) is 2.60 +/- 0.01 A. Structural comparisons show that the side chain of the catalytic base (Glu167) can move during the reaction cycle in a small cavity, located above the hydroxamate plane. The structure analysis suggests that the hydroxamate moiety of PGH is negatively charged. Therefore, the bound PGH mimics the negatively charged enediolate intermediate, which is formed immediately after the initial proton abstraction from DHAP by the catalytic glutamate. The new findings are discussed in the context of the current knowledge of the TIM reaction mechanism.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21236668 A.Yep, R.J.Sorenson, M.R.Wilson, H.D.Showalter, S.D.Larsen, P.R.Keller, and R.W.Woodard (2011).
Enediol mimics as inhibitors of the D-arabinose 5-phosphate isomerase (KdsD) from Francisella tularensis.
  Bioorg Med Chem Lett, 21, 2679-2682.  
20694739 R.K.Wierenga, E.G.Kapetaniou, and R.Venkatesan (2010).
Triosephosphate isomerase: a highly evolved biocatalyst.
  Cell Mol Life Sci, 67, 3961-3982.  
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.