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PDBsum entry 1tpv

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Isomerase(intramolecular oxidoreductase) PDB id
1tpv
Jmol
Contents
Protein chains
245 a.a. *
Ligands
PGH ×2
Waters ×249
* Residue conservation analysis
PDB id:
1tpv
Name: Isomerase(intramolecular oxidoreductase)
Title: S96p change is a second-site suppressor for h95n sluggish mu triosephosphate isomerase
Structure: Triosephosphate isomerase. Chain: a, b. Engineered: yes. Mutation: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.183    
Authors: Z.Zhang,S.Sugio,E.A.Komives,K.D.Liu,A.M.Stock,N.Narayana,Ng. J.R.Knowles,G.A.Petsko,D.Ringe
Key ref:
E.A.Komives et al. (1996). The structural basis for pseudoreversion of the H95N lesion by the secondary S96P mutation in triosephosphate isomerase. Biochemistry, 35, 15474-15484. PubMed id: 8952501 DOI: 10.1021/bi961556v
Date:
07-Nov-94     Release date:   20-Apr-95    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00940  (TPIS_CHICK) -  Triosephosphate isomerase
Seq:
Struc:
248 a.a.
245 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   4 terms 
  Biological process     metabolic process   9 terms 
  Biochemical function     catalytic activity     3 terms  

 

 
DOI no: 10.1021/bi961556v Biochemistry 35:15474-15484 (1996)
PubMed id: 8952501  
 
 
The structural basis for pseudoreversion of the H95N lesion by the secondary S96P mutation in triosephosphate isomerase.
E.A.Komives, J.C.Lougheed, Z.Zhang, S.Sugio, N.Narayana, N.H.Xuong, G.A.Petsko, D.Ringe.
 
  ABSTRACT  
 
The structural basis for the 3000-fold decrease in catalytic efficiency of the H95N mutant chicken triosephosphate isomerase and the 60-fold regain of catalytic efficiency in the double mutant, H95N.S96P, have been analyzed. The results from a combination of X-ray crystallography and Fourier transform infrared spectroscopy experiments indicate that the predominant defect in the H95N mutant isomerase appears to be its inability to bind the substrate in a coplanar, cis conformation. The structures of each mutant isomerase were determined from X-ray crystallography of the complex of phosphoglycolohydroxamate (PGH), an intermediate analog with the isomerase, and each was solved to a resolution of 1.9 A. The PGH appeared to be in two different conformations in which the enediol-mimicking atoms, O2-N2-C1-O1, of the PGH were not coplanar. No density was observed that would correspond to the coplanar conformation. Two bands are observed for the dihydroxyacetone phosphate carbonyl in the H95N mutant FTIR spectrum, and these can be explained if the O1 of DHAP, like the O1 of PGH in the crystal structure, is in two different positions. Two ordered water molecules are located between O1 of PGH and N delta of N95. Comparison of the structure of the pseudorevertant, H95N.S96P with that for the H95N single mutant, shows that S96P mutation causes the double mutant to regain the ability to bind PGH predominantly in the coplanar, cis conformation. Electron density for a single ordered water molecule bridging the N95 amide side chain and the O2 of PGH is observed, but the density was weak, perhaps indicating that the water molecule is somewhat disordered. Whether or not a water molecule is hydrogen bonded to O2 of PGH may explain the two carbonyl stretching frequencies observed for the GAP carbonyl. Together, the crystal structures and the FTIR data allow a complete explanation of the catalytic properties of these two mutant isomerases.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
17287353 S.Rozovsky, and A.E.McDermott (2007).
Substrate product equilibrium on a reversible enzyme, triosephosphate isomerase.
  Proc Natl Acad Sci U S A, 104, 2080-2085.  
15796706 R.A.Friesner, and V.Guallar (2005).
Ab initio quantum chemical and mixed quantum mechanics/molecular mechanics (QM/MM) methods for studying enzymatic catalysis.
  Annu Rev Phys Chem, 56, 389-427.  
12509510 G.Jogl, S.Rozovsky, A.E.McDermott, and L.Tong (2003).
Optimal alignment for enzymatic proton transfer: structure of the Michaelis complex of triosephosphate isomerase at 1.2-A resolution.
  Proc Natl Acad Sci U S A, 100, 50-55.
PDB codes: 1ney 1nf0
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