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PDBsum entry 7tim

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protein ligands Protein-protein interface(s) links
Intramolecular oxidoreductase PDB id
7tim
Jmol
Contents
Protein chains
247 a.a. *
Ligands
PGH ×2
Waters ×247
* Residue conservation analysis
PDB id:
7tim
Name: Intramolecular oxidoreductase
Title: Structure of the triosephosphate isomerase- phosphoglycolohydroxamate complex: an analogue of the intermediate on the reaction pathway
Structure: Triosephosphate isomerase. Chain: a, b. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.183    
Authors: R.C.Davenport,P.A.Bash,B.A.Seaton,M.Karplus,G.A.Petsko, D.Ringe
Key ref:
R.C.Davenport et al. (1991). Structure of the triosephosphate isomerase-phosphoglycolohydroxamate complex: an analogue of the intermediate on the reaction pathway. Biochemistry, 30, 5821-5826. PubMed id: 2043623 DOI: 10.1021/bi00238a002
Date:
23-Apr-91     Release date:   31-Oct-93    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00942  (TPIS_YEAST) -  Triosephosphate isomerase
Seq:
Struc:
248 a.a.
247 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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 66.00% similarity
= glycerone phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrion   1 term 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     3 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/bi00238a002 Biochemistry 30:5821-5826 (1991)
PubMed id: 2043623  
 
 
Structure of the triosephosphate isomerase-phosphoglycolohydroxamate complex: an analogue of the intermediate on the reaction pathway.
R.C.Davenport, P.A.Bash, B.A.Seaton, M.Karplus, G.A.Petsko, D.Ringe.
 
  ABSTRACT  
 
The glycolytic enzyme triosephosphate isomerase (TIM) catalyzes the interconversion of the three-carbon sugars dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP) at a rate limited by the diffusion of substrate to the enzyme. We have solved the three-dimensional structure of TIM complexed with a reactive intermediate analogue, phosphoglycolohydroxamate (PGH), at 1.9-A resolution and have refined the structure to an R-factor of 18%. Analysis of the refined structure reveals the geometry of the active-site residues and the interactions they make with the inhibitor and, by analogy, the substrates. The structure is consistent with an acid-base mechanism in which the carboxylate of Glu-165 abstracts a proton from carbon while His-95 donates a proton to oxygen to form an enediol (or enediolate) intermediate. The conformation of the bound substrate stereoelectronically favors proton transfer from substrate carbon to the syn orbital of Glu-165. The crystal structure suggests that His-95 is neutral rather than cationic in the ground state and therefore would have to function as an imidazole acid instead of the usual imidazolium. Lys-12 is oriented so as to polarize the substrate oxygens by hydrogen bonding and/or electrostatic interaction, providing stabilization for the charged transition state. Asn-10 may play a similar role.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21058398 C.Roux, F.Bhatt, J.Foret, B.de Courcy, N.Gresh, J.P.Piquemal, C.J.Jeffery, and L.Salmon (2011).
The reaction mechanism of type I phosphomannose isomerases: new information from inhibition and polarizable molecular mechanics studies.
  Proteins, 79, 203-220.  
20694739 R.K.Wierenga, E.G.Kapetaniou, and R.Venkatesan (2010).
Triosephosphate isomerase: a highly evolved biocatalyst.
  Cell Mol Life Sci, 67, 3961-3982.  
19938875 Y.L.Lin, and J.Gao (2010).
Internal proton transfer in the external pyridoxal 5'-phosphate Schiff base in dopa decarboxylase.
  Biochemistry, 49, 84-94.  
19425580 M.K.Go, T.L.Amyes, and J.P.Richard (2009).
Hydron transfer catalyzed by triosephosphate isomerase. Products of the direct and phosphite-activated isomerization of [1-(13)C]-glycolaldehyde in D(2)O.
  Biochemistry, 48, 5769-5778.  
19089986 S.Donnini, A.Villa, G.Groenhof, A.E.Mark, R.K.Wierenga, and A.H.Juffer (2009).
Inclusion of ionization states of ligands in affinity calculations.
  Proteins, 76, 138-150.  
  19342791 S.Mukherjee, D.Dutta, B.Saha, and A.K.Das (2009).
Expression, purification, crystallization and preliminary X-ray diffraction studies of triosephosphate isomerase from methicillin-resistant Staphylococcus aureus (MRSA252).
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 398-401.  
18700786 K.K.Chan, A.A.Fedorov, E.V.Fedorov, S.C.Almo, and J.A.Gerlt (2008).
Structural basis for substrate specificity in phosphate binding (beta/alpha)8-barrels: D-allulose 6-phosphate 3-epimerase from Escherichia coli K-12.
  Biochemistry, 47, 9608-9617.
PDB codes: 3ct7 3ctl
18376850 W.Y.Tsang, T.L.Amyes, and J.P.Richard (2008).
A substrate in pieces: allosteric activation of glycerol 3-phosphate dehydrogenase (NAD+) by phosphite dianion.
  Biochemistry, 47, 4575-4582.  
17381236 I.N.Berezovsky, K.B.Zeldovich, and E.I.Shakhnovich (2007).
Positive and negative design in stability and thermal adaptation of natural proteins.
  PLoS Comput Biol, 3, e52.  
17336327 J.G.Kempf, J.Y.Jung, C.Ragain, N.S.Sampson, and J.P.Loria (2007).
Dynamic requirements for a functional protein hinge.
  J Mol Biol, 368, 131-149.  
17935329 S.Ma, L.S.Devi-Kesavan, and J.Gao (2007).
Molecular dynamics simulations of the catalytic pathway of a cysteine protease: a combined QM/MM study of human cathepsin K.
  J Am Chem Soc, 129, 13633-13645.  
17444661 T.L.Amyes, and J.P.Richard (2007).
Enzymatic catalysis of proton transfer at carbon: activation of triosephosphate isomerase by phosphite dianion.
  Biochemistry, 46, 5841-5854.  
16323206 F.A.Konuklar, V.Aviyente, and T.Halilo─člu (2006).
Coupling of structural fluctuations to deamidation reaction in triosephosphate isomerase by Gaussian network model.
  Proteins, 62, 715-727.  
16517612 I.A.Rose (2006).
Mechanistic inferences from stereochemistry.
  J Biol Chem, 281, 6117-6119.  
16741995 S.Donnini, G.Groenhof, R.K.Wierenga, and A.H.Juffer (2006).
The planar conformation of a strained proline ring: a QM/MM study.
  Proteins, 64, 700-710.  
15590681 A.K.Roos, E.Burgos, D.J.Ericsson, L.Salmon, and S.L.Mowbray (2005).
Competitive inhibitors of Mycobacterium tuberculosis ribose-5-phosphate isomerase B reveal new information about the reaction mechanism.
  J Biol Chem, 280, 6416-6422.
PDB codes: 2bes 2bet
14988504 L.Zheng, U.Baumann, and J.L.Reymond (2004).
Molecular mechanism of enantioselective proton transfer to carbon in catalytic antibody 14D9.
  Proc Natl Acad Sci U S A, 101, 3387-3392.
PDB codes: 1uwe 1uwg
12483674 G.Alagona, C.Ghio, and P.A.Kollman (2003).
The intramolecular mechanism for the second proton transfer in triosephosphate isomerase (TIM): a QM/FE approach.
  J Comput Chem, 24, 46-56.  
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
14563846 S.Parthasarathy, K.Eaazhisai, H.Balaram, P.Balaram, and M.R.Murthy (2003).
Structure of Plasmodium falciparum triose-phosphate isomerase-2-phosphoglycerate complex at 1.1-A resolution.
  J Biol Chem, 278, 52461-52470.
PDB code: 1o5x
12552084 W.Yang, Y.Q.Gao, Q.Cui, J.Ma, and M.Karplus (2003).
The missing link between thermodynamics and structure in F1-ATPase.
  Proc Natl Acad Sci U S A, 100, 874-879.  
11983887 D.Arsenieva, R.Hardre, L.Salmon, and C.J.Jeffery (2002).
The crystal structure of rabbit phosphoglucose isomerase complexed with 5-phospho-D-arabinonohydroxamic acid.
  Proc Natl Acad Sci U S A, 99, 5872-5877.
PDB code: 1koj
12185208 J.A.Silverman, and P.B.Harbury (2002).
Rapid mapping of protein structure, interactions, and ligand binding by misincorporation proton-alkyl exchange.
  J Biol Chem, 277, 30968-30975.  
11389594 G.T.Marks, T.K.Harris, M.A.Massiah, A.S.Mildvan, and D.H.Harrison (2001).
Mechanistic implications of methylglyoxal synthase complexed with phosphoglycolohydroxamic acid as observed by X-ray crystallography and NMR spectroscopy.
  Biochemistry, 40, 6805-6818.
PDB code: 1ik4
11589711 I.Kursula, S.Partanen, A.M.Lambeir, D.M.Antonov, K.Augustyns, and R.K.Wierenga (2001).
Structural determinants for ligand binding and catalysis of triosephosphate isomerase.
  Eur J Biochem, 268, 5189-5196.
PDB code: 1if2
11248037 J.A.Silverman, R.Balakrishnan, and P.B.Harbury (2001).
Reverse engineering the (beta/alpha )8 barrel fold.
  Proc Natl Acad Sci U S A, 98, 3092-3097.  
10963661 B.Golinelli-Pimpaneau, O.Goncalves, T.Dintinger, D.Blanchard, M.Knossow, and C.Tellier (2000).
Structural evidence for a programmed general base in the active site of a catalytic antibody.
  Proc Natl Acad Sci U S A, 97, 9892-9895.
PDB code: 1f3d
10715115 D.Saadat, and D.H.Harrison (2000).
Mirroring perfection: the structure of methylglyoxal synthase complexed with the competitive inhibitor 2-phosphoglycolate.
  Biochemistry, 39, 2950-2960.
PDB code: 1egh
11114510 H.Erlandsen, E.E.Abola, and R.C.Stevens (2000).
Combining structural genomics and enzymology: completing the picture in metabolic pathways and enzyme active sites.
  Curr Opin Struct Biol, 10, 719-730.  
10576923 R.Hardré, and L.Salmon (1999).
Competitive inhibitors of yeast phosphoglucose isomerase: synthesis and evaluation of new types of phosphorylated sugars from the synthon D-arabinolactone-5-phosphate.
  Carbohydr Res, 318, 110-115.  
10194326 R.Pérez-Montfort, G.Garza-Ramos, G.H.Alcántara, H.Reyes-Vivas, X.G.Gao, E.Maldonado, M.T.de Gómez-Puyou, and A.Gómez-Puyou (1999).
Derivatization of the interface cysteine of triosephosphate isomerase from Trypanosoma brucei and Trypanosoma cruzi as probe of the interrelationship between the catalytic sites and the dimer interface.
  Biochemistry, 38, 4114-4120.  
10328262 T.K.Harris, and A.S.Mildvan (1999).
High-precision measurement of hydrogen bond lengths in proteins by nuclear magnetic resonance methods.
  Proteins, 35, 275-282.  
10194358 Z.Zhang, E.A.Komives, S.Sugio, S.C.Blacklow, N.Narayana, N.H.Xuong, A.M.Stock, G.A.Petsko, and D.Ringe (1999).
The role of water in the catalytic efficiency of triosephosphate isomerase.
  Biochemistry, 38, 4389-4397.
PDB code: 1tpw
9556344 J.P.Richard (1998).
The enhancement of enzymatic rate accelerations by Brønsted acid-base catalysis.
  Biochemistry, 37, 4305-4309.  
9873748 R.Hardré, C.Bonnette, L.Salmon, and A.Gaudemer (1998).
Synthesis and evaluation of a new inhibitor of phosphoglucose isomerases: the enediolate analogue 5-phospho-D-arabinohydroxamate.
  Bioorg Med Chem Lett, 8, 3435-3438.  
9843453 T.K.Harris, R.N.Cole, F.I.Comer, and A.S.Mildvan (1998).
Proton transfer in the mechanism of triosephosphate isomerase.
  Biochemistry, 37, 16828-16838.  
9348662 C.L.Perrin, and J.B.Nielson (1997).
"Strong" hydrogen bonds in chemistry and biology.
  Annu Rev Phys Chem, 48, 511-544.  
8952501 E.A.Komives, J.C.Lougheed, Z.Zhang, S.Sugio, N.Narayana, N.H.Xuong, G.A.Petsko, and D.Ringe (1996).
The structural basis for pseudoreversion of the H95N lesion by the secondary S96P mutation in triosephosphate isomerase.
  Biochemistry, 35, 15474-15484.
PDB codes: 1tpu 1tpv
8626554 J.Aqvist, and M.Fothergill (1996).
Computer simulation of the triosephosphate isomerase catalyzed reaction.
  J Biol Chem, 271, 10010-10016.  
8841131 W.C.Alston, M.Kanska, and C.J.Murray (1996).
Secondary H/T and D/T isotope effects in enzymatic enolization reactions. Coupled motion and tunneling in the triosephosphate isomerase reaction.
  Biochemistry, 35, 12873-12881.  
  8745400 W.Schliebs, N.Thanki, R.Eritja, and R.Wierenga (1996).
Active site properties of monomeric triosephosphate isomerase (monoTIM) as deduced from mutational and structural studies.
  Protein Sci, 5, 229-239.  
8789193 C.S.Poornima, and P.M.Dean (1995).
Hydration in drug design. 2. Influence of local site surface shape on water binding.
  J Comput Aided Mol Des, 9, 513-520.  
  8580851 L.F.Delboni, S.C.Mande, F.Rentier-Delrue, V.Mainfroid, S.Turley, F.M.Vellieux, J.A.Martial, and W.G.Hol (1995).
Crystal structure of recombinant triosephosphate isomerase from Bacillus stearothermophilus. An analysis of potential thermostability factors in six isomerases with known three-dimensional structures points to the importance of hydrophobic interactions.
  Protein Sci, 4, 2594-2604.
PDB code: 1btm
  8061610 S.C.Mande, V.Mainfroid, K.H.Kalk, K.Goraj, J.A.Martial, and W.G.Hol (1994).
Crystal structure of recombinant human triosephosphate isomerase at 2.8 A resolution. Triosephosphate isomerase-related human genetic disorders and comparison with the trypanosomal enzyme.
  Protein Sci, 3, 810-821.
PDB code: 1hti
8356028 M.E.Noble, J.P.Zeelen, and R.K.Wierenga (1993).
Structures of the "open" and "closed" state of trypanosomal triosephosphate isomerase, as observed in a new crystal form: implications for the reaction mechanism.
  Proteins, 16, 311-326.
PDB codes: 1tpd 1trd 2v5l
  1304889 C.L.Verlinde, C.J.Witmans, T.Pijning, K.H.Kalk, W.G.Hol, M.Callens, and F.R.Opperdoes (1992).
Structure of the complex between trypanosomal triosephosphate isomerase and N-hydroxy-4-phosphono-butanamide: binding at the active site despite an "open" flexible loop conformation.
  Protein Sci, 1, 1578-1584.
PDB code: 1tsi
1639191 R.K.Wierenga, T.V.Borchert, and M.E.Noble (1992).
Crystallographic binding studies with triosephosphate isomerases: conformational changes induced by substrate and substrate-analogues.
  FEBS Lett, 307, 34-39.  
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 codes are shown on the right.