PDBsum entry 1s5m

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Isomerase PDB id
Protein chain
386 a.a. *
_NA ×2
_MN ×2
Waters ×424
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Xylose isomerase in substrate and inhibitor michaelis states resolution studies of a metal-mediated hydride shift
Structure: Xylose isomerase. Chain: a. Engineered: yes
Source: Streptomyces olivochromogenes. Organism_taxid: 1963. Gene: xyla. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
0.98Å     R-factor:   0.111     R-free:   0.129
Authors: T.D.Fenn,D.Ringe,G.A.Petsko
Key ref:
T.D.Fenn et al. (2004). Xylose isomerase in substrate and inhibitor michaelis states: atomic resolution studies of a metal-mediated hydride shift. Biochemistry, 43, 6464-6474. PubMed id: 15157080 DOI: 10.1021/bi049812o
21-Jan-04     Release date:   10-Feb-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P15587  (XYLA_STROL) -  Xylose isomerase
387 a.a.
386 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.  - Xylose isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: D-xylopyranose = D-xylulose
Bound ligand (Het Group name = GLC)
matches with 83.33% 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/bi049812o Biochemistry 43:6464-6474 (2004)
PubMed id: 15157080  
Xylose isomerase in substrate and inhibitor michaelis states: atomic resolution studies of a metal-mediated hydride shift.
T.D.Fenn, D.Ringe, G.A.Petsko.
Xylose isomerase (E.C. catalyzes the interconversion of aldose and ketose sugars and has an absolute requirement for two divalent cations at its active site to drive the hydride transfer rates of sugar isomerization. Evidence suggests some degree of metal movement at the second metal site, although how this movement may affect catalysis is unknown. The 0.95 A resolution structure of the xylitol-inhibited enzyme presented here suggests three alternative positions for the second metal ion, only one of which appears positioned in a catalytically competent manner. To complete the reaction, an active site hydroxyl species appears appropriately positioned for hydrogen transfer, as evidenced by precise bonding distances. Conversely, the 0.98 A resolution structure of the enzyme with glucose bound in the alpha-pyranose state only shows one of the metal ion conformations at the second metal ion binding site, suggesting that the linear form of the sugar is required to promote the second and third metal ion conformations. The two structures suggest a strong degree of conformational flexibility at the active site, which seems required for catalysis and may explain the poor rate of turnover for this enzyme. Further, the pyranose structure implies that His53 may act as the initial acid responsible for ring opening of the sugar to the aldose form, an observation that has been difficult to establish in previous studies. The glucose ring also appears to display significant segmented disorder in a manner suggestive of ring opening, perhaps lending insight into means of enzyme destabilization of the ground state to promote catalysis. On the basis of these results, we propose a modified version of the bridged bimetallic mechanism for hydride transfer in the case of Streptomyces olivochromogenes xylose isomerase.

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.  
21481775 T.D.Fenn, M.J.Schnieders, M.Mustyakimov, C.Wu, P.Langan, V.S.Pande, and A.T.Brunger (2011).
Reintroducing electrostatics into macromolecular crystallographic refinement: application to neutron crystallography and DNA hydration.
  Structure, 19, 523-533.
PDB code: 3qba
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
20541500 B.C.Bennett, and M.Yeager (2010).
The lighter side of a sweet reaction.
  Structure, 18, 657-659.  
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
20694739 R.K.Wierenga, E.G.Kapetaniou, and R.Venkatesan (2010).
Triosephosphate isomerase: a highly evolved biocatalyst.
  Cell Mol Life Sci, 67, 3961-3982.  
18578508 A.Y.Kovalevsky, A.K.Katz, H.L.Carrell, L.Hanson, M.Mustyakimov, S.Z.Fisher, L.Coates, B.P.Schoenborn, G.J.Bunick, J.P.Glusker, and P.Langan (2008).
Hydrogen location in stages of an enzyme-catalyzed reaction: time-of-flight neutron structure of D-xylose isomerase with bound D-xylulose.
  Biochemistry, 47, 7595-7597.
PDB code: 3cwh
18156470 H.Tamura, Y.Saito, H.Ashida, T.Inoue, Y.Kai, A.Yokota, and H.Matsumura (2008).
Crystal structure of 5-methylthioribose 1-phosphate isomerase product complex from Bacillus subtilis: implications for catalytic mechanism.
  Protein Sci, 17, 126-135.
PDB codes: 2yrf 2yvk
18586714 I.Georgiev, D.Keedy, J.S.Richardson, D.C.Richardson, and B.R.Donald (2008).
Algorithm for backrub motions in protein design.
  Bioinformatics, 24, i196-i204.  
17203501 M.A.Borgi, M.Rhimi, and S.Bejar (2007).
Involvement of alanine 103 residue in kinetic and physicochemical properties of glucose isomerases from Streptomyces species.
  Biotechnol J, 2, 254-259.  
17337581 M.Rhimi, M.Juy, N.Aghajari, R.Haser, and S.Bejar (2007).
Probing the essential catalytic residues and substrate affinity in the thermoactive Bacillus stearothermophilus US100 L-arabinose isomerase by site-directed mutagenesis.
  J Bacteriol, 189, 3556-3563.  
17690466 Y.Saito, H.Ashida, C.Kojima, H.Tamura, H.Matsumura, Y.Kai, and A.Yokota (2007).
Enzymatic characterization of 5-methylthioribose 1-phosphate isomerase from Bacillus subtilis.
  Biosci Biotechnol Biochem, 71, 2021-2028.  
16724195 E.H.Snell, M.J.van der Woerd, M.Damon, R.A.Judge, D.A.Myles, and F.Meilleur (2006).
Optimizing crystal volume for neutron diffraction: D-xylose isomerase.
  Eur Biophys J, 35, 621-632.  
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.  
16768441 L.Williams, T.Nguyen, Y.Li, T.N.Porter, and F.M.Raushel (2006).
Uronate isomerase: a nonhydrolytic member of the amidohydrolase superfamily with an ambivalent requirement for a divalent metal ion.
  Biochemistry, 45, 7453-7462.  
16114036 L.R.Forrest, and B.Honig (2005).
An assessment of the accuracy of methods for predicting hydrogen positions in protein structures.
  Proteins, 61, 296-309.  
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.  
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.