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PDBsum entry 1lbm

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Isomerase PDB id
1lbm
Jmol
Contents
Protein chain
194 a.a. *
Ligands
137
Waters ×69
* Residue conservation analysis
PDB id:
1lbm
Name: Isomerase
Title: Crystal structure of phosphoribosyl anthranilate isomerase ( complex with reduced 1-(o-carboxyphenylamino)-1-deoxyribulo phosphate (rcdrp)
Structure: Phosphoribosyl anthranilate isomerase. Chain: a. Engineered: yes
Source: Thermotoga maritima. Organism_taxid: 2336. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.80Å     R-factor:   0.170     R-free:   0.228
Authors: M.Hennig,R.Sterner,K.Kirschner
Key ref:
M.Henn-Sax et al. (2002). Two (betaalpha)(8)-barrel enzymes of histidine and tryptophan biosynthesis have similar reaction mechanisms and common strategies for protecting their labile substrates. Biochemistry, 41, 12032-12042. PubMed id: 12356303 DOI: 10.1021/bi026092h
Date:
04-Apr-02     Release date:   18-Dec-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q56320  (TRPF_THEMA) -  N-(5'-phosphoribosyl)anthranilate isomerase
Seq:
Struc:
205 a.a.
194 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.5.3.1.24  - Phosphoribosylanthranilate isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Tryptophan Biosynthesis
      Reaction: N-(5-phospho-beta-D-ribosyl)anthranilate = 1-(2-carboxyphenylamino)-1- deoxy-D-ribulose 5-phosphate
N-(5-phospho-beta-D-ribosyl)anthranilate
Bound ligand (Het Group name = 137)
corresponds exactly
= 1-(2-carboxyphenylamino)-1- deoxy-D-ribulose 5-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     3 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/bi026092h Biochemistry 41:12032-12042 (2002)
PubMed id: 12356303  
 
 
Two (betaalpha)(8)-barrel enzymes of histidine and tryptophan biosynthesis have similar reaction mechanisms and common strategies for protecting their labile substrates.
M.Henn-Sax, R.Thoma, S.Schmidt, M.Hennig, K.Kirschner, R.Sterner.
 
  ABSTRACT  
 
The enzymes N'-[(5'-phosphoribosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide isomerase (HisA) and phosphoribosylanthranilate isomerase (TrpF) are sugar isomerases that are involved in histidine and tryptophan biosynthesis, respectively. Both enzymes have the (betaalpha)(8)-barrel fold and catalyze Amadori rearrangements of a thermolabile aminoaldose into the corresponding aminoketose. To identify those amino acids that are essential for catalysis, conserved residues at the active sites of both HisA and TrpF from the hyperthermophile Thermotoga maritima were replaced by site-directed mutagenesis, and the purified variants were investigated by steady-state enzyme kinetics. Aspartate 8, aspartate 127, and threonine 164 appeared to be important for the HisA reaction, whereas cysteine 7 and aspartate 126 appeared to be important for the TrpF reaction. On the basis of these results and the X-ray structure of a complex between TrpF and a bound product analogue, a reaction mechanism involving general acid-base catalysis and a Schiff base intermediate is proposed for both enzymes. A comparison of the HisA and TrpF enzymes from T. maritima and Escherichia coli showed that, at the physiological temperatures of 80 and 37 degrees C, respectively, the enzymes from the hyperthermophile have significantly higher catalytic efficiencies than the corresponding enzymes from mesophiles. These results suggest that HisA and TrpF have similar chemical reaction mechanisms and use the same strategy to prevent the loss of their thermolabile substrates.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21321225 A.V.Due, J.Kuper, A.Geerlof, J.P.Kries, and M.Wilmanns (2011).
Bisubstrate specificity in histidine/tryptophan biosynthesis isomerase from Mycobacterium tuberculosis by active site metamorphosis.
  Proc Natl Acad Sci U S A, 108, 3554-3559.
PDB codes: 2y85 2y88 2y89
21354426 S.Setiyaputra, J.P.Mackay, and W.M.Patrick (2011).
The structure of a truncated phosphoribosylanthranilate isomerase suggests a unified model for evolution of the (βα)8 barrel fold.
  J Mol Biol, 408, 291-303.
PDB code: 2kzh
  20066665 L.Noda-García, A.R.Camacho-Zarco, K.Verdel-Aranda, H.Wright, X.Soberón, V.Fülöp, and F.Barona-Gómez (2010).
Identification and analysis of residues contained on beta --> alpha loops of the dual-substrate (beta alpha)8 phosphoribosyl isomerase A specific for its phosphoribosyl anthranilate isomerase activity.
  Protein Sci, 19, 535-543.
PDB code: 2x30
19208235 A.Fischer, N.Enkler, G.Neudert, M.Bocola, R.Sterner, and R.Merkl (2009).
TransCent: computational enzyme design by transferring active sites and considering constraints relevant for catalysis.
  BMC Bioinformatics, 10, 54.  
19237570 J.Claren, C.Malisi, B.Höcker, and R.Sterner (2009).
Establishing wild-type levels of catalytic activity on natural and artificial (beta alpha)8-barrel protein scaffolds.
  Proc Natl Acad Sci U S A, 106, 3704-3709.
PDB code: 2w79
18272177 W.M.Patrick, and I.Matsumura (2008).
A study in molecular contingency: glutamine phosphoribosylpyrophosphate amidotransferase is a promiscuous and evolvable phosphoribosylanthranilate isomerase.
  J Mol Biol, 377, 323-336.  
16731983 S.Quevillon-Cheruel, N.Leulliot, M.Graille, K.Blondeau, J.Janin, and H.van Tilbeurgh (2006).
Crystal structure of the yeast His6 enzyme suggests a reaction mechanism.
  Protein Sci, 15, 1516-1521.
PDB code: 2agk
15857781 B.Höcker (2005).
Directed evolution of (betaalpha)(8)-barrel enzymes.
  Biomol Eng, 22, 31-38.  
15654319 J.Kuper, C.Doenges, and M.Wilmanns (2005).
Two-fold repeated (betaalpha)4 half-barrels may provide a molecular tool for dual substrate specificity.
  EMBO Rep, 6, 134-139.
PDB code: 1vzw
15539462 B.Höcker, J.Claren, and R.Sterner (2004).
Mimicking enzyme evolution by generating new (betaalpha)8-barrels from (betaalpha)4-half-barrels.
  Proc Natl Acad Sci U S A, 101, 16448-16453.  
14993684 H.Wright, F.Barona-Gómez, D.A.Hodgson, and V.Fülöp (2004).
Expression, purification and preliminary crystallographic analysis of phosphoribosyl isomerase (PriA) from Streptomyces coelicolor.
  Acta Crystallogr D Biol Crystallogr, 60, 534-536.  
12634849 F.Barona-Gómez, and D.A.Hodgson (2003).
Occurrence of a putative ancient-like isomerase involved in histidine and tryptophan biosynthesis.
  EMBO Rep, 4, 296-300.  
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 codes are shown on the right.