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PDBsum entry 2fpx

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
2fpx
Jmol
Contents
Protein chains
156 a.a. *
160 a.a. *
Ligands
SO4
Metals
_MG ×3
_ZN ×2
Waters ×513
* Residue conservation analysis
PDB id:
2fpx
Name: Hydrolase
Title: Crystal structure of the n-terminal domain of e.Coli hisb- s complex.
Structure: Histidine biosynthesis bifunctional protein hisb. Chain: a, b. Fragment: n-terminal domain, histidinol-phosphatase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 83334. Strain: o157:h7. Gene: hisb. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PQS)
Resolution:
1.80Å     R-factor:   0.179     R-free:   0.213
Authors: E.S Rangarajan,M.Cygler,A.Matte,Montreal-Kingston Bacterial Structural Genomics Initiative (Bsgi)
Key ref:
E.S.Rangarajan et al. (2006). Structural snapshots of Escherichia coli histidinol phosphate phosphatase along the reaction pathway. J Biol Chem, 281, 37930-37941. PubMed id: 16966333 DOI: 10.1074/jbc.M604916200
Date:
17-Jan-06     Release date:   05-Sep-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9S5G5  (HIS7_ECO57) -  Histidine biosynthesis bifunctional protein HisB
Seq:
Struc:
355 a.a.
156 a.a.
Protein chain
Pfam   ArchSchema ?
Q9S5G5  (HIS7_ECO57) -  Histidine biosynthesis bifunctional protein HisB
Seq:
Struc:
355 a.a.
160 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: Chains A, B: E.C.3.1.3.15  - Histidinol-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Histidine Biosynthesis (late stages)
      Reaction: L-histidinol phosphate + H2O = L-histidinol + phosphate
L-histidinol phosphate
+ H(2)O
= L-histidinol
+ phosphate
   Enzyme class 2: Chains A, B: E.C.4.2.1.19  - Imidazoleglycerol-phosphate dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
      Reaction: D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate = 3-(imidazol-4-yl)-2- oxopropyl phosphate + H2O
D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate
= 3-(imidazol-4-yl)-2- oxopropyl phosphate
+ H(2)O
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
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   2 terms 
  Biochemical function     imidazoleglycerol-phosphate dehydratase activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M604916200 J Biol Chem 281:37930-37941 (2006)
PubMed id: 16966333  
 
 
Structural snapshots of Escherichia coli histidinol phosphate phosphatase along the reaction pathway.
E.S.Rangarajan, A.Proteau, J.Wagner, M.N.Hung, A.Matte, M.Cygler.
 
  ABSTRACT  
 
HisB from Escherichia coli is a bifunctional enzyme catalyzing the sixth and eighth steps of l-histidine biosynthesis. The N-terminal domain (HisB-N) possesses histidinol phosphate phosphatase activity, and its crystal structure shows a single domain with fold similarity to the haloacid dehalogenase (HAD) enzyme family. HisB-N forms dimers in the crystal and in solution. The structure shows the presence of a structural Zn(2+) ion stabilizing the conformation of an extended loop. Two metal binding sites were also identified in the active site. Their presence was further confirmed by isothermal titration calorimetry. HisB-N is active in the presence of Mg(2+), Mn(2+), Co(2+), or Zn(2+), but Ca(2+) has an inhibitory effect. We have determined structures of several intermediate states corresponding to snapshots along the reaction pathway, including that of the phosphoaspartate intermediate. A catalytic mechanism, different from that described for other HAD enzymes, is proposed requiring the presence of the second metal ion not found in the active sites of previously characterized HAD enzymes, to complete the second half-reaction. The proposed mechanism is reminiscent of two-Mg(2+) ion catalysis utilized by DNA and RNA polymerases and many nucleases. The structure also provides an explanation for the inhibitory effect of Ca(2+).
 
  Selected figure(s)  
 
Figure 5.
FIGURE 5. a, states along the reaction pathway based on determined structures. I, the initial state with site 1 occupied by Mg^2+; II, HisB-N with histidinol phosphate substrate modeled on the structure of histidinol complex; III, phosphoaspartate intermediate with Mg^2+ occupying sites 1 and 2; IV, release of phosphate and Mg^2+ from site 2; b, superposition of the active site residues of HisB-N (gray) with E. coli AphA (orange). Red spheres represent water molecules; violet spheres show metal binding sites. The orientations of Asp^12 and its equivalent in AphA are different. Asp^12 is stabilized by hydrogen bonds (blue) to Arg^11, site 2, and bridging water W4. Asp^46 of AphA is hydrogen-bonded (orange) to Arg^114, approaching from the opposite direction to Arg^11 of HisB-N, and to the of phosphate oxygen in the position of water W1. Only HisB residues are labeled.
Figure 6.
FIGURE 6. Changes in the HisB-N substrate binding region along the reaction pathway shown in a surface representation. The residues that undergo conformational changes due to binding of the substrate and/or metal ions, namely Glu^18, Phe^23, and Arg^132 are shown as sticks under semitransparent surface. All structures are shown in the same orientation. a, HisB-N·Mg; b, HisB-N·Mg/histidinol; c, HisB-N·Ca/pAsp; and d, HisB-N·Mg/sulfate.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 37930-37941) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20050614 H.H.Nguyen, L.Wang, H.Huang, E.Peisach, D.Dunaway-Mariano, and K.N.Allen (2010).
Structural determinants of substrate recognition in the HAD superfamily member D-glycero-D-manno-heptose-1,7-bisphosphate phosphatase (GmhB) .
  Biochemistry, 49, 1082-1092.
PDB codes: 3l8e 3l8f 3l8g 3l8h
20050615 L.Wang, H.Huang, H.H.Nguyen, K.N.Allen, P.S.Mariano, and D.Dunaway-Mariano (2010).
Divergence of biochemical function in the HAD superfamily: D-glycero-D-manno-heptose-1,7-bisphosphate phosphatase (GmhB).
  Biochemistry, 49, 1072-1081.  
19889535 K.N.Allen, and D.Dunaway-Mariano (2009).
Markers of fitness in a successful enzyme superfamily.
  Curr Opin Struct Biol, 19, 658-665.  
18223080 H.S.Lee, Y.Cho, J.H.Lee, and S.G.Kang (2008).
Novel monofunctional histidinol-phosphate phosphatase of the DDDD superfamily of phosphohydrolases.
  J Bacteriol, 190, 2629-2632.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
  19052358 R.Schnell, D.Agren, and G.Schneider (2008).
1.9 A structure of the signal receiver domain of the putative response regulator NarL from Mycobacterium tuberculosis.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1096-1100.
PDB code: 3eul
17668295 A.Matte, Z.Jia, S.Sunita, J.Sivaraman, and M.Cygler (2007).
Insights into the biology of Escherichia coli through structural proteomics.
  J Struct Funct Genomics, 8, 45-55.  
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.