PDBsum entry 2gyi

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Isomerase(intramolecular oxidoreductase) PDB id
Protein chains
385 a.a. *
HYA ×2
_MG ×4
Waters ×634
* Residue conservation analysis
PDB id:
Name: Isomerase(intramolecular oxidoreductase)
Title: Design, synthesis, and characterization of a potent xylose i inhibitor, d-threonohydroxamic acid, and high-resolution x- crystallographic structure of the enzyme-inhibitor complex
Structure: Xylose isomerase. Chain: a, b. Engineered: yes
Source: Streptomyces olivochromogenes. Organism_taxid: 1963
Biol. unit: Tetramer (from PQS)
1.60Å     R-factor:   0.216    
Authors: K.N.Allen,A.Lavie,G.A.Petsko,D.Ringe
Key ref:
K.N.Allen et al. (1995). Design, synthesis, and characterization of a potent xylose isomerase inhibitor, D-threonohydroxamic acid, and high-resolution X-ray crystallographic structure of the enzyme-inhibitor complex. Biochemistry, 34, 3742-3749. PubMed id: 7893671 DOI: 10.1021/bi00011a032
01-Sep-94     Release date:   10-Jul-95    
Supersedes: 1gyi
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P15587  (XYLA_STROL) -  Xylose isomerase
387 a.a.
385 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Xylose isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: D-xylopyranose = D-xylulose
Bound ligand (Het Group name = HYA)
matches with 66.67% similarity
= D-xylulose
      Cofactor: Mg(2+)
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     carbohydrate metabolic process   3 terms 
  Biochemical function     isomerase activity     4 terms  


    Key reference    
DOI no: 10.1021/bi00011a032 Biochemistry 34:3742-3749 (1995)
PubMed id: 7893671  
Design, synthesis, and characterization of a potent xylose isomerase inhibitor, D-threonohydroxamic acid, and high-resolution X-ray crystallographic structure of the enzyme-inhibitor complex.
K.N.Allen, A.Lavie, G.A.Petsko, D.Ringe.
The binding of a potent inhibitor to the enzyme D-xylose isomerase from Streptomyces olivochromogenes was examined by kinetics and X-ray crystallography. The inhibitor D-threonohydroxamic acid (THA) was designed to mimic the putative transition state of the isomerization step catalyzed by the enzyme on the substrate xylose. THA was synthesized and found to be a slow-binding competitive inhibitor with the substrate glucose. The Ki < or = 100 nM was at least one million-fold less than the KM for glucose. The X-ray crystallographic structure of xylose isomerase with THA soaked into the crystals (concentration = 1000Ki) was obtained to 1.6-A resolution and refined to an R factor of 21.6%. The free enzyme and the enzyme in the xylose isomerase-THA complex show no significant structural differences. THA binds in an analogous fashion to glucose, in a linear conformation, forming ligands with Mg-1 and Mg-2 and hydrogen bonds with His53 and Lys182. On the basis of these similarities to glucose binding and its potent inhibition, we propose that THA resembles the transition state for the enzyme-catalyzed hydride transfer reaction. The THA C2 hydroxyl forms a bridging ligand between Mg-1 and Mg-2; it must be deprotonated to do so. By analogy, we propose that, during the catalytic reaction, C2 of the substrate glucose is deprotonated, and that this proton can be moved to the C1 hydroxyl concomitant with hydride transfer. We find evidence for metal movement during catalysis upon deprotonation of the C2 hydroxyl, to allow formation of a bridging ligand.(ABSTRACT TRUNCATED AT 250 WORDS)

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.  
21058398 C.Roux, F.Bhatt, J.Foret, 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.  
21429479 M.Bera, and A.Patra (2011).
Study of potential binding of biologically important sugars with a dinuclear cobalt(II) complex.
  Carbohydr Res, 346, 733-738.  
19172689 M.Pellecchia, I.Bertini, D.Cowburn, C.Dalvit, E.Giralt, W.Jahnke, T.L.James, S.W.Homans, H.Kessler, C.Luchinat, B.Meyer, H.Oschkinat, J.Peng, H.Schwalbe, and G.Siegal (2008).
Perspectives on NMR in drug discovery: a technique comes of age.
  Nat Rev Drug Discov, 7, 738-745.  
17640070 S.Vincenzetti, B.Quadrini, P.Mariani, G.De Sanctis, N.Cammertoni, V.Polzonetti, S.Pucciarelli, P.Natalini, and A.Vita (2008).
Modulation of human cytidine deaminase by specific aminoacids involved in the intersubunit interactions.
  Proteins, 70, 144-156.  
16235215 R.Kappl, K.Ranguelova, B.Koch, C.Duboc, and J.Hüttermann (2005).
Multi-frequency high-field EPR studies on metal-substituted xylose isomerase.
  Magn Reson Chem, 43, S65-S73.  
15322278 M.Garcia-Viloca, T.D.Poulsen, D.G.Truhlar, and J.Gao (2004).
Sensitivity of molecular dynamics simulations to the choice of the X-ray structure used to model an enzymatic reaction.
  Protein Sci, 13, 2341-2354.  
12497598 M.Garcia-Viloca, C.Alhambra, D.G.Truhlar, and J.Gao (2003).
Hydride transfer catalyzed by xylose isomerase: mechanism and quantum effects.
  J Comput Chem, 24, 177-190.  
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
11434371 A.Burger, D.Tritsch, and J.F.Biellmann (2001).
Di-tert-butyl diethylphosphoramidite as the phosphitylating reagent in the preparation of 3-deoxy-3-C-methylene-D-ribo-hexose-6-phosphate and 3-deoxy-3-C-methylene-D-erythro-pentose-5-phosphate.
  Carbohydr Res, 332, 141-149.  
10666592 X.Zhu, M.Teng, L.Niu, C.Xu, and Y.Wang (2000).
Structure of xylose isomerase from Streptomyces diastaticus no. 7 strain M1033 at 1.85 A resolution.
  Acta Crystallogr D Biol Crystallogr, 56, 129-136.
PDB codes: 1clk 1qt1
10089429 C.Chang, H.K.Song, B.C.Park, D.S.Lee, and S.W.Suh (1999).
A thermostable xylose isomerase from Thermus caldophilus: biochemical characterization, crystallization and preliminary X-ray analysis.
  Acta Crystallogr D Biol Crystallogr, 55, 294-296.  
10318897 Y.J.Sun, C.C.Chou, W.S.Chen, R.T.Wu, M.Meng, and C.D.Hsiao (1999).
The crystal structure of a multifunctional protein: phosphoglucose isomerase/autocrine motility factor/neuroleukin.
  Proc Natl Acad Sci U S A, 96, 5412-5417.
PDB code: 2pgi
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.  
9201965 M.A.Pearson, L.O.Michel, R.P.Hausinger, and P.A.Karplus (1997).
Structures of Cys319 variants and acetohydroxamate-inhibited Klebsiella aerogenes urease.
  Biochemistry, 36, 8164-8172.
PDB codes: 1fwa 1fwb 1fwc 1fwd 1fwe 1fwf 1fwg 1fwh 1fwj
9188736 M.Fuxreiter, Z.Böcskei, A.Szeibert, E.Szabó, G.Dallmann, G.Naray-Szabo, and B.Asboth (1997).
Role of electrostatics at the catalytic metal binding site in xylose isomerase action: Ca(2+)-inhibition and metal competence in the double mutant D254E/D256E.
  Proteins, 28, 183-193.  
  8801434 S.H.Bhosale, M.B.Rao, and V.V.Deshpande (1996).
Molecular and industrial aspects of glucose isomerase.
  Microbiol Rev, 60, 280-300.  
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.