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PDBsum entry 1rzm

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
1rzm
Jmol
Contents
Protein chains
338 a.a. *
Ligands
PEP ×2
E4P ×2
Metals
_CD ×3
Waters ×159
* Residue conservation analysis
PDB id:
1rzm
Name: Transferase
Title: Crystal structure of 3-deoxy-d-arabino-heptulosonate-7-phosp synthase (dahps) from thermotoga maritima complexed with cd and e4p
Structure: Phospho-2-dehydro-3-deoxyheptonate aldolase. Chain: a, b. Synonym: phospho-2- keto-3-deoxyheptonate aldolase, dahp sy 3-deoxy-d-arabino- heptulosonate 7-phosphate synthase. Engineered: yes
Source: Thermotoga maritima. Organism_taxid: 2336. Gene: arof, tm0343. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.20Å     R-factor:   0.219     R-free:   0.251
Authors: I.A.Shumilin,R.Bauerle,J.Wu,R.W.Woodard,R.H.Kretsinger
Key ref:
I.A.Shumilin et al. (2004). Crystal structure of the reaction complex of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Thermotoga maritima refines the catalytic mechanism and indicates a new mechanism of allosteric regulation. J Mol Biol, 341, 455-466. PubMed id: 15276836 DOI: 10.1016/j.jmb.2004.05.077
Date:
24-Dec-03     Release date:   10-Aug-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9WYH8  (AROF_THEMA) -  Phospho-2-dehydro-3-deoxyheptonate aldolase
Seq:
Struc:
338 a.a.
338 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.5.1.54  - 3-deoxy-7-phosphoheptulonate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Shikimate and Chorismate Biosynthesis
      Reaction: Phosphoenolpyruvate + D-erythrose 4-phosphate + H2O = 3-deoxy-D- arabino-hept-2-ulosonate 7-phosphate + phosphate
Phosphoenolpyruvate
Bound ligand (Het Group name = PEP)
corresponds exactly
+
D-erythrose 4-phosphate
Bound ligand (Het Group name = E4P)
corresponds exactly
+ H(2)O
= 3-deoxy-D- arabino-hept-2-ulosonate 7-phosphate
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     biosynthetic process   4 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2004.05.077 J Mol Biol 341:455-466 (2004)
PubMed id: 15276836  
 
 
Crystal structure of the reaction complex of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Thermotoga maritima refines the catalytic mechanism and indicates a new mechanism of allosteric regulation.
I.A.Shumilin, R.Bauerle, J.Wu, R.W.Woodard, R.H.Kretsinger.
 
  ABSTRACT  
 
3-Deoxy-d-arabino-heptulosonate-7-phosphate synthase (DAHPS) catalyzes the first reaction of the aromatic biosynthetic pathway in bacteria, fungi, and plants, the condensation of phosphoenolpyruvate (PEP) and d-erythrose-4-phosphate (E4P) with the formation of DAHP. Crystals of DAHPS from Thermotoga maritima (DAHPS(Tm)) were grown in the presence of PEP and metal cofactor, Cd(2+), and then soaked with E4P at 4 degrees C where the catalytic activity of the enzyme is negligible. The crystal structure of the "frozen" reaction complex was determined at 2.2A resolution. The subunit of the DAHPS(Tm) homotetramer consists of an N-terminal ferredoxin-like (FL) domain and a (beta/alpha)(8)-barrel domain. The active site located at the C-end of the barrel contains Cd(2+), PEP, and E4P, the latter bound in a non-productive conformation. The productive conformation of E4P is suggested and a catalytic mechanism of DAHPS is proposed. The active site of DAHPS(Tm) is nearly identical to the active sites of the other two known DAHPS structures from Escherichia coli (DAHPS(Ec)) and Saccharomyces cerevisiae (DAHPS(Sc)). However, the secondary, tertiary, and quaternary structures of DAHPS(Tm) are more similar to the functionally related enzyme, 3-deoxy-d-manno-octulosonate-8-phosphate synthase (KDOPS) from E.coli and Aquiflex aeolicus, than to DAHPS(Ec) and DAHPS(Sc). Although DAHPS(Tm) is feedback-regulated by tyrosine and phenylalanine, it lacks the extra barrel segments that are required for feedback inhibition in DAHPS(Ec) and DAHPS(Sc). A sequence similarity search revealed that DAHPSs of phylogenetic family Ibeta possess a FL domain like DAHPS(Tm) while those of family Ialpha have extra barrel segments similar to those of DAHPS(Ec) and DAHPS(Sc). This indicates that the mechanism of feedback regulation in DAHPS(Tm) and other family Ibeta enzymes is different from that of family Ialpha enzymes, most likely being mediated by the FL domain.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. The coordination of (a) PEP, (b) E4P and A5P, and (c) metal cations in the active sites of DAHPSTm, DAHPSEc, and KDOPSAa. PEP and E4P/G3P/A5P observed in the crystal structures are purple/green. The modeled productive E4P conformation in DAHPSTm and DAHPSEc (b) is purple/orange. Coordinating residues are in gray, metal cofactors cyan, and water molecules red. The coordinating interactions are shown as black dotted lines.
Figure 6.
Figure 6. Modeling of the E4P binding in the productive complex and the catalytic mechanism of DAHPS. (a) The conformation of E4P in the active site of DAHPSTm-Cd-PEP-E4P (Figure 2(b)) is modified by rotation around its s-bonds. Steric conflict between the O3 hydroxyl of E4P and a water molecule is shown as a red dotted line. (b) The immediate participants of the DAHPS reaction. H-bonds and the O1(E4P)-Cd^2+ bond are shown as black dotted lines. The green dotted line connects the substrate atoms forming the covalent bond in the condensation reaction. (c) The suggested catalytic mechanism of DAHPS. The metal ion is not shown but it probably plays a role in the activation of the E4P aldehyde group. H-bonds are shown as black dotted lines.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 341, 455-466) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20517625 S.Tapas, G.Kumar Patel, S.Dhindwal, and S.Tomar (2011).
In Silico sequence analysis and molecular modeling of the three-dimensional structure of DAHP synthase from Pseudomonas fragi.
  J Mol Model, 17, 621-631.  
19473543 M.Aklujkar, J.Krushkal, G.DiBartolo, A.Lapidus, M.L.Land, and D.R.Lovley (2009).
The genome sequence of Geobacter metallireducens: features of metabolism, physiology and regulation common and dissimilar to Geobacter sulfurreducens.
  BMC Microbiol, 9, 109.  
16339761 J.Wu, and R.W.Woodard (2006).
New insights into the evolutionary links relating to the 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase subfamilies.
  J Biol Chem, 281, 4042-4048.  
17064285 S.B.Conners, E.F.Mongodin, M.R.Johnson, C.I.Montero, K.E.Nelson, and R.M.Kelly (2006).
Microbial biochemistry, physiology, and biotechnology of hyperthermophilic Thermotoga species.
  FEMS Microbiol Rev, 30, 872-905.  
  16511053 C.J.Webby, J.S.Lott, H.M.Baker, E.N.Baker, and E.J.Parker (2005).
Crystallization and preliminary X-ray crystallographic analysis of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Mycobacterium tuberculosis.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 403-406.  
15516336 J.Gunawan, D.Simard, M.Gilbert, A.L.Lovering, W.W.Wakarchuk, M.E.Tanner, and N.C.Strynadka (2005).
Structural and mechanistic analysis of sialic acid synthase NeuB from Neisseria meningitidis in complex with Mn2+, phosphoenolpyruvate, and N-acetylmannosaminitol.
  J Biol Chem, 280, 3555-3563.
PDB codes: 1xuu 1xuz
16267580 M.Ahn, A.L.Pietersma, L.R.Schofield, and E.J.Parker (2005).
Mechanistic divergence of two closely related aldol-like enzyme-catalysed reactions.
  Org Biomol Chem, 3, 4046-4049.  
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.