PDBsum entry 4xis

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Isomerase(intramolecular oxidoreductase) PDB id
Protein chain
387 a.a. *
_MN ×2
Waters ×404
* Residue conservation analysis
PDB id:
Name: Isomerase(intramolecular oxidoreductase)
Title: A metal-mediated hydride shift mechanism for xylose isomeras the 1.6 angstroms streptomyces rubiginosus structures with and d-xylose
Structure: Xylose isomerase. Chain: a. Engineered: yes
Source: Streptomyces rubiginosus. Organism_taxid: 1929
Biol. unit: Tetramer (from PQS)
1.60Å     R-factor:   0.135    
Authors: M.Whitlow,A.J.Howard
Key ref: M.Whitlow et al. (1991). A metal-mediated hydride shift mechanism for xylose isomerase based on the 1.6 A Streptomyces rubiginosus structures with xylitol and D-xylose. Proteins, 9, 153-173. PubMed id: 2006134
25-Mar-91     Release date:   15-Jul-92    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P24300  (XYLA_STRRU) -  Xylose isomerase
388 a.a.
387 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 = XLS)
corresponds exactly
= 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    
Proteins 9:153-173 (1991)
PubMed id: 2006134  
A metal-mediated hydride shift mechanism for xylose isomerase based on the 1.6 A Streptomyces rubiginosus structures with xylitol and D-xylose.
M.Whitlow, A.J.Howard, B.C.Finzel, T.L.Poulos, E.Winborne, G.L.Gilliland.
The crystal structure of recombinant Streptomyces rubiginosus D-xylose isomerase (D-xylose keto-isomerase, EC solved by the multiple isomorphous replacement technique has been refined to R = 0.16 at 1.64 A resolution. As observed in an earlier study at 4.0 A (Carrell et al., J. Biol. Chem. 259: 3230-3236, 1984), xylose isomerase is a tetramer composed of four identical subunits. The monomer consists of an eight-stranded parallel beta-barrel surrounded by eight helices with an extended C-terminal tail that provides extensive contacts with a neighboring monomer. The active site pocket is defined by an opening in the barrel whose entrance is lined with hydrophobic residues while the bottom of the pocket consists mainly of glutamate, aspartate, and histidine residues coordinated to two manganese ions. The structures of the enzyme in the presence of MnCl2, the inhibitor xylitol, and the substrate D-xylose in the presence and absence of MnCl2 have also been refined to R = 0.14 at 1.60 A, R = 0.15 at 1.71 A, R = 0.15 at 1.60 A, and R = 0.14 at 1.60 A, respectively. Both the ring oxygen of the cyclic alpha-D-xylose and its C1 hydroxyl are within hydrogen bonding distance of NE2 of His-54 in the structure crystallized in the presence of D-xylose. Both the inhibitor, xylitol, and the extended form of the substrate, D-xylose, bind such that the C2 and C4 OH groups interact with one of the two divalent cations found in the active site and the C1 OH with the other cation. The remainder of the OH groups hydrogen bond with neighboring amino acid side chains. A detailed mechanism for D-xylose isomerase is proposed. Upon binding of cyclic alpha-D-xylose to xylose isomerase, His-54 acts as the catalytic base in a ring opening reaction. The ring opening step is followed by binding of D-xylose, involving two divalent cations, in an extended conformation. The isomerization of D-xylose to D-xylulose involves a metal-mediated 1,2-hydride shift. The final step in the mechanism is a ring closure to produce alpha-D-xylulose. The ring closing is the reverse of the ring opening step. This mechanism accounts for the majority of xylose isomerase's biochemical properties, including (1) the lack of solvent exchange between the 2-position of D-xylose and the 1-pro-R position of D-xylulose, (2) the chemical modification of histidine and lysine, (3) the pH vs. activity profile, and (4) the requirement for two divalent cations in the mechanism.

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
20852996 P.Prabhu, T.T.Doan, M.Jeya, L.W.Kang, and J.K.Lee (2011).
Cloning and characterization of a rhamnose isomerase from Bacillus halodurans.
  Appl Microbiol Biotechnol, 89, 635-644.  
21268148 T.Ståhlberg, S.Rodriguez-Rodriguez, P.Fristrup, and A.Riisager (2011).
Metal-free dehydration of glucose to 5-(hydroxymethyl)furfural in ionic liquids with boric acid as a promoter.
  Chemistry, 17, 1456-1464.  
20541506 A.Y.Kovalevsky, L.Hanson, S.Z.Fisher, M.Mustyakimov, S.A.Mason, V.T.Forsyth, M.P.Blakeley, D.A.Keen, T.Wagner, H.L.Carrell, A.K.Katz, J.P.Glusker, and P.Langan (2010).
Metal ion roles and the movement of hydrogen during reaction catalyzed by D-xylose isomerase: a joint x-ray and neutron diffraction study.
  Structure, 18, 688-699.
PDB codes: 3kbm 3kbn 3kbs 3kbv 3kbw 3kcl 3kco
20977999 H.Yoshida, K.Takeda, K.Izumori, and S.Kamitori (2010).
Elucidation of the role of Ser329 and the C-terminal region in the catalytic activity of pseudomonas stutzeri L-rhamnose isomerase.
  Protein Eng Des Sel, 23, 919-927.
PDB codes: 3m0h 3m0l 3m0m 3m0v 3m0x 3m0y
20088877 H.Yoshida, M.Yamaji, T.Ishii, K.Izumori, and S.Kamitori (2010).
Catalytic reaction mechanism of Pseudomonas stutzeri L-rhamnose isomerase deduced from X-ray structures.
  FEBS J, 277, 1045-1057.
PDB codes: 3itl 3ito 3itt 3itv 3itx 3ity 3iud 3iuh 3iui
  18931442 K.Takeda, H.Yoshida, G.Takada, K.Izumori, and S.Kamitori (2008).
Overexpression, purification, crystallization and preliminary X-ray crystal analysis of Bacillus pallidusD-arabinose isomerase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 945-948.  
18849419 R.Shi, M.Pineda, E.Ajamian, Q.Cui, A.Matte, and M.Cygler (2008).
Structure of L-xylulose-5-Phosphate 3-epimerase (UlaE) from the anaerobic L-ascorbate utilization pathway of Escherichia coli: identification of a novel phosphate binding motif within a TIM barrel fold.
  J Bacteriol, 190, 8137-8144.
PDB codes: 3cqh 3cqi 3cqj 3cqk
16673077 F.Meilleur, E.H.Snell, M.J.van der Woerd, R.A.Judge, and D.A.Myles (2006).
A quasi-Laue neutron crystallographic study of D-xylose isomerase.
  Eur Biophys J, 35, 601-609.  
  16754978 H.Yoshida, P.Wayoon, G.Takada, K.Izumori, and S.Kamitori (2006).
Crystallization and preliminary X-ray diffraction studies of L-rhamnose isomerase from Pseudomonas stutzeri.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 550-552.  
15752361 K.L.Epting, C.Vieille, J.G.Zeikus, and R.M.Kelly (2005).
Influence of divalent cations on the structural thermostability and thermal inactivation kinetics of class II xylose isomerases.
  FEBS J, 272, 1454-1464.  
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.  
16336264 T.Hansen, B.Schlichting, J.Grötzinger, M.K.Swan, C.Davies, and P.Schönheit (2005).
Mutagenesis of catalytically important residues of cupin type phosphoglucose isomerase from Archaeoglobus fulgidus.
  FEBS J, 272, 6266-6275.  
14747699 B.L.Hanson, P.Langan, A.K.Katz, X.Li, J.M.Harp, J.P.Glusker, B.P.Schoenborn, and G.J.Bunick (2004).
A preliminary time-of-flight neutron diffraction study of Streptomyces rubiginosus D-xylose isomerase.
  Acta Crystallogr D Biol Crystallogr, 60, 241-249.  
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.  
12595702 C.Davies, and H.Muirhead (2003).
Structure of native phosphoglucose isomerase from rabbit: conformational changes associated with catalytic function.
  Acta Crystallogr D Biol Crystallogr, 59, 453-465.
PDB code: 1n8t
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.  
12970347 M.K.Swan, J.T.Solomons, C.C.Beeson, T.Hansen, P.Schönheit, and C.Davies (2003).
Structural evidence for a hydride transfer mechanism of catalysis in phosphoglucose isomerase from Pyrococcus furiosus.
  J Biol Chem, 278, 47261-47268.
PDB codes: 1qxj 1qxr 1qy4
12531907 N.L.Que-Gewirth, S.Lin, R.J.Cotter, and C.R.Raetz (2003).
An outer membrane enzyme that generates the 2-amino-2-deoxy-gluconate moiety of Rhizobium leguminosarum lipid A.
  J Biol Chem, 278, 12109-12119.  
11784309 A.Lönn, M.Gárdonyi, W.van Zyl, B.Hahn-Hägerdal, and R.C.Otero (2002).
Cold adaptation of xylose isomerase from Thermus thermophilus through random PCR mutagenesis. Gene cloning and protein characterization.
  Eur J Biochem, 269, 157-163.  
11972016 J.Gao, and D.G.Truhlar (2002).
Quantum mechanical methods for enzyme kinetics.
  Annu Rev Phys Chem, 53, 467-505.  
12112707 R.G.Zhang, I.Dementieva, N.Duke, F.Collart, E.Quaite-Randall, R.Alkire, L.Dieckman, N.Maltsev, O.Korolev, and A.Joachimiak (2002).
Crystal structure of Bacillus subtilis ioli shows endonuclase IV fold with altered Zn binding.
  Proteins, 48, 423-426.
PDB codes: 1i60 1i6n
11238984 C.Vieille, and G.J.Zeikus (2001).
Hyperthermophilic enzymes: sources, uses, and molecular mechanisms for thermostability.
  Microbiol Mol Biol Rev, 65, 1.  
11733026 C.Vieille, K.L.Epting, R.M.Kelly, and J.G.Zeikus (2001).
Bivalent cations and amino-acid composition contribute to the thermostability of Bacillus licheniformis xylose isomerase.
  Eur J Biochem, 268, 6291-6301.  
11440117 T.Kaneko, K.Saito, Y.Kawamura, and S.Takahashi (2001).
Molecular cloning of acid-stable glucose isomerase gene from Streptomyces olivaceoviridis E-86 by a simple two-step PCR method, and its expression in Escherichia coli.
  Biosci Biotechnol Biochem, 65, 1054-1062.  
11454337 T.Tanase, T.Takei, M.Hidai, and S.Yano (2001).
Substrate-dependent chemoselective aldose-aldose and aldose-ketose isomerizations of carbohydrates promoted by a combination of calcium ion and monoamines.
  Carbohydr Res, 333, 303-312.  
10966417 K.A.Erlandson, J.H.Park, Wissam, El Khal, H.H.Kao, P.Basaran, S.Brydges, and C.A.Batt (2000).
Dissolution of xylose metabolism in Lactococcus lactis.
  Appl Environ Microbiol, 66, 3974-3980.  
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.  
  9647799 J.M.Hess, V.Tchernajenko, C.Vieille, J.G.Zeikus, and R.M.Kelly (1998).
Thermotoga neapolitana homotetrameric xylose isomerase is expressed as a catalytically active and thermostable dimer in Escherichia coli.
  Appl Environ Microbiol, 64, 2357-2360.  
9298953 G.M.Ananyev, and G.C.Dismukes (1997).
Calcium induces binding and formation of a spin-coupled dimanganese(II,II) center in the apo-water oxidation complex of photosystem II as precursor to the functional tetra-Mn/Ca cluster.
  Biochemistry, 36, 11342-11350.  
9141134 H.Hu, H.Liu, and Y.Shi (1997).
The reaction pathway of the isomerization of D-xylose catalyzed by the enzyme D-xylose isomerase: a theoretical study.
  Proteins, 27, 545-555.  
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.  
9054539 R.Bogumil, R.Kappl, J.Hüttermann, and H.Witzel (1997).
Electron paramagnetic resonance of D-xylose isomerase: evidence for metal ion movement induced by binding of cyclic substrates and inhibitors.
  Biochemistry, 36, 2345-2352.  
8916223 H.Hu, Y.Y.Shi, and C.X.Wang (1996).
Exploring the interaction between D-xylose isomerase and D-xylose by free energy calculation.
  Proteins, 26, 157-166.  
  8830690 S.Y.Liu, J.Wiegel, and F.C.Gherardini (1996).
Purification and cloning of a thermostable xylose (glucose) isomerase with an acidic pH optimum from Thermoanaerobacterium strain JW/SL-YS 489.
  J Bacteriol, 178, 5938-5945.  
7784428 D.W.Deerfield, D.J.Fox, M.Head-Gordon, R.G.Hiskey, and L.G.Pedersen (1995).
The first solvation shell of magnesium ion in a model protein environment with formate, water, and X-NH3, H2S, imidazole, formaldehyde, and chloride as ligands: an Ab initio study.
  Proteins, 21, 244-255.  
8378319 M.Meng, M.Bagdasarian, and J.G.Zeikus (1993).
The role of active-site aromatic and polar residues in catalysis and substrate discrimination by xylose isomerase.
  Proc Natl Acad Sci U S A, 90, 8459-8463.  
8389296 R.Bogumil, R.Kappl, J.Hüttermann, C.Sudfeldt, and H.Witzel (1993).
X- and Q-band EPR studies on the two Mn(2+)-substituted metal-binding sites of D-xylose isomerase.
  Eur J Biochem, 213, 1185-1192.  
  1657868 H.C.Wong, Y.Ting, H.C.Lin, F.Reichert, K.Myambo, K.W.Watt, P.L.Toy, and R.J.Drummond (1991).
Genetic organization and regulation of the xylose degradation genes in Streptomyces rubiginosus.
  J Bacteriol, 173, 6849-6858.  
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.