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PDBsum entry 1otg

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protein ligands Protein-protein interface(s) links
Isomerase PDB id
1otg
Jmol
Contents
Protein chains
125 a.a. *
Ligands
SO4 ×7
Waters ×201
* Residue conservation analysis
PDB id:
1otg
Name: Isomerase
Title: 5-carboxymethyl-2-hydroxymuconate isomerase
Structure: 5-carboxymethyl-2-hydroxymuconate isomerase. Chain: a, b, c. Engineered: yes
Source: Escherichia coli. Organism_taxid: 498388. Strain: c. Gene: chm. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: chmi promoter
Biol. unit: Trimer (from PQS)
Resolution:
2.10Å     R-factor:   0.179    
Authors: H.S.Subramanya,D.I.Roper,Z.Dauter,E.J.Dodson,G.J.Davies,K.S. D.B.Wigley
Key ref:
H.S.Subramanya et al. (1996). Enzymatic ketonization of 2-hydroxymuconate: specificity and mechanism investigated by the crystal structures of two isomerases. Biochemistry, 35, 792-802. PubMed id: 8547259 DOI: 10.1021/bi951732k
Date:
09-Nov-95     Release date:   03-Apr-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q05354  (HPCD_ECOLX) -  5-carboxymethyl-2-hydroxymuconate Delta-isomerase
Seq:
Struc:
126 a.a.
125 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.5.3.3.10  - 5-carboxymethyl-2-hydroxymuconate Delta-isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 5-carboxymethyl-2-hydroxymuconate = 5-carboxy-2-oxohept-3-enedioate
5-carboxymethyl-2-hydroxymuconate
= 5-carboxy-2-oxohept-3-enedioate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     aromatic compound catabolic process   1 term 
  Biochemical function     isomerase activity     2 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/bi951732k Biochemistry 35:792-802 (1996)
PubMed id: 8547259  
 
 
Enzymatic ketonization of 2-hydroxymuconate: specificity and mechanism investigated by the crystal structures of two isomerases.
H.S.Subramanya, D.I.Roper, Z.Dauter, E.J.Dodson, G.J.Davies, K.S.Wilson, D.B.Wigley.
 
  ABSTRACT  
 
5-Carboxymethyl-2-hydroxymuconate isomerase (CHMI) and 4-oxalocrotonate tautomerase (4-OT) are enzymes that catalyze the isomerization of unsaturated ketones. They share a common enzyme mechanism, although they show a preference for different substrates. There is no apparent sequence homology between the enzymes. To investigate the molecular mechanism and the basis for their substrate specificity, we have determined the crystal structures of the two enzymes at high resolution. 4-OT is hexameric, with the subunits arranged with 32 symmetry. CHMI is trimeric and has extensive contacts between subunits, which include secondary structural elements. The central core of the CHMI monomer has a fold similar to a 4-OT dimer, but the secondary structural elements that form the subunit contacts around the 3-fold axis are different in the two enzymes. The region of greatest similarity between the two enzymes is a large pocket that is proposed to be the active site. The enzymes appear to operate via a "one-base" mechanism, and the possible role of residues in this pocket is discussed in view of this idea. Finally, the molecular basis for substrate specificity in the two enzymes is discussed.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21219457 J.Nogales, A.Canales, J.Jiménez-Barbero, B.Serra, J.M.Pingarrón, J.L.García, and E.Díaz (2011).
Unravelling the gallic acid degradation pathway in bacteria: the gal cluster from Pseudomonas putida.
  Mol Microbiol, 79, 359-374.  
21048922 M.Andreatta, M.Nielsen, F.Møller Aarestrup, and O.Lund (2010).
In silico prediction of human pathogenicity in the γ-proteobacteria.
  PLoS One, 5, e13680.  
19199636 J.J.Ruiz-Pernía, M.Garcia-Viloca, S.Bhattacharyya, J.Gao, D.G.Truhlar, and I.Tuñón (2009).
Critical role of substrate conformational change in the proton transfer process catalyzed by 4-oxalocrotonate tautomerase.
  J Am Chem Soc, 131, 2687-2698.  
19437047 P.E.Siegbahn, and F.Himo (2009).
Recent developments of the quantum chemical cluster approach for modeling enzyme reactions.
  J Biol Inorg Chem, 14, 643-651.  
18695941 G.J.Poelarends, V.P.Veetil, and C.P.Whitman (2008).
The chemical versatility of the beta-alpha-beta fold: catalytic promiscuity and divergent evolution in the tautomerase superfamily.
  Cell Mol Life Sci, 65, 3606-3618.  
17121835 R.M.de Jong, P.Bazzacco, G.J.Poelarends, W.H.Johnson, Y.J.Kim, E.A.Burks, H.Serrano, A.M.Thunnissen, C.P.Whitman, and B.W.Dijkstra (2007).
Crystal structures of native and inactivated cis-3-chloroacrylic acid dehalogenase. Structural basis for substrate specificity and inactivation by (R)-oxirane-2-carboxylate.
  J Biol Chem, 282, 2440-2449.
PDB codes: 2flt 2flz
17902707 S.C.Wang, W.H.Johnson, R.M.Czerwinski, S.L.Stamps, and C.P.Whitman (2007).
Kinetic and stereochemical analysis of YwhB, a 4-oxalocrotonate tautomerase homologue in Bacillus subtilis: mechanistic implications for the YwhB- and 4-oxalocrotonate tautomerase-catalyzed reactions.
  Biochemistry, 46, 11919-11929.  
16784221 G.J.Poelarends, J.J.Almrud, H.Serrano, J.E.Darty, W.H.Johnson, M.L.Hackert, and C.P.Whitman (2006).
Evolution of enzymatic activity in the tautomerase superfamily: mechanistic and structural consequences of the L8R mutation in 4-oxalocrotonate tautomerase.
  Biochemistry, 45, 7700-7708.
PDB code: 2fm7
  17012798 T.Adachi, A.Izumi, D.Rea, S.Y.Park, J.R.Tame, and D.I.Roper (2006).
Expression, purification and crystallization of 2-oxo-hept-4-ene-1,7-dioate hydratase (HpcG) from Escherichia coli C.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 1010-1012.  
  16511168 D.Rea, V.Fülöp, T.D.Bugg, and D.I.Roper (2005).
Expression, purification and preliminary crystallographic analysis of 2,4-dihydroxy-hepta-2-ene-1,7-dioate aldolase (HpcH) from Escherichia coli C.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 821-824.  
14701869 R.M.de Jong, W.Brugman, G.J.Poelarends, C.P.Whitman, and B.W.Dijkstra (2004).
The X-ray structure of trans-3-chloroacrylic acid dehalogenase reveals a novel hydration mechanism in the tautomerase superfamily.
  J Biol Chem, 279, 11546-11552.
PDB code: 1s0y
12823441 B.Sonesson, E.Rosengren, A.S.Hansson, and C.Hansson (2003).
UVB-induced inflammation gives increased d-dopachrome tautomerase activity in blister fluid which correlates with macrophage migration inhibitory factor.
  Exp Dermatol, 12, 278-282.  
12667094 E.Lolis, and R.Bucala (2003).
Macrophage migration inhibitory factor.
  Expert Opin Ther Targets, 7, 153-164.  
12792855 T.Calandra, C.Froidevaux, C.Martin, and T.Roger (2003).
Macrophage migration inhibitory factor and host innate immune defenses against bacterial sepsis.
  J Infect Dis, 187, S385-S390.  
12454498 A.Wright, A.Blewett, V.Fulop, R.Cooper, S.Burrows, C.Jones, and D.Roper (2002).
Expression, purification, crystallization and preliminary characterization of an HHED aldolase homologue from Escherichia coli K12.
  Acta Crystallogr D Biol Crystallogr, 58, 2191-2193.  
12084071 E.Machado Benelli, M.Buck, I.Polikarpov, E.Maltempi de Souza, L.M.Cruz, and F.O.Pedrosa (2002).
Herbaspirillum seropedicae signal transduction protein PII is structurally similar to the enteric GlnK.
  Eur J Biochem, 269, 3296-3303.
PDB code: 1hwu
11782558 J.A.Baugh, and R.Bucala (2002).
Macrophage migration inhibitory factor.
  Crit Care Med, 30, S27-S35.  
11997397 J.B.Lubetsky, A.Dios, J.Han, B.Aljabari, B.Ruzsicska, R.Mitchell, E.Lolis, and Y.Al-Abed (2002).
The tautomerase active site of macrophage migration inhibitory factor is a potential target for discovery of novel anti-inflammatory agents.
  J Biol Chem, 277, 24976-24982.
PDB code: 1ljt
11863436 J.R.Tame, K.Namba, E.J.Dodson, and D.I.Roper (2002).
The crystal structure of HpcE, a bifunctional decarboxylase/isomerase with a multifunctional fold.
  Biochemistry, 41, 2982-2989.
PDB codes: 1gtt 1i7o
12382291 T.A.Soares, R.D.Lins, T.P.Straatsma, and J.M.Briggs (2002).
Internal dynamics and ionization states of the macrophage migration inhibitory factor: comparison between wild-type and mutant forms.
  Biopolymers, 65, 313-323.  
11729263 E.Díaz, A.Ferrández, M.A.Prieto, and J.L.García (2001).
Biodegradation of aromatic compounds by Escherichia coli.
  Microbiol Mol Biol Rev, 65, 523.  
11418568 G.J.Poelarends, R.Saunier, and D.B.Janssen (2001).
trans-3-Chloroacrylic acid dehalogenase from Pseudomonas pavonaceae 170 shares structural and mechanistic similarities with 4-oxalocrotonate tautomerase.
  J Bacteriol, 183, 4269-4277.  
11488984 G.R.Fingerle-Rowson, and R.Bucala (2001).
Neuroendocrine properties of macrophage migration inhibitory factor (MIF).
  Immunol Cell Biol, 79, 368-375.  
11329265 R.M.Czerwinski, T.K.Harris, M.A.Massiah, A.S.Mildvan, and C.P.Whitman (2001).
The structural basis for the perturbed pKa of the catalytic base in 4-oxalocrotonate tautomerase: kinetic and structural effects of mutations of Phe-50.
  Biochemistry, 40, 1984-1995.  
  11152126 B.E.Ramirez, O.N.Voloshin, R.D.Camerini-Otero, and A.Bax (2000).
Solution structure of DinI provides insight into its mode of RecA inactivation.
  Protein Sci, 9, 2161-2169.
PDB codes: 1f0a 1ghh
10933783 S.L.Stamps, A.B.Taylor, S.C.Wang, M.L.Hackert, and C.P.Whitman (2000).
Mechanism of the phenylpyruvate tautomerase activity of macrophage migration inhibitory factor: properties of the P1G, P1A, Y95F, and N97A mutants.
  Biochemistry, 39, 9671-9678.
PDB code: 1mff
10360941 A.B.Taylor, W.H.Johnson, R.M.Czerwinski, H.S.Li, M.L.Hackert, and C.P.Whitman (1999).
Crystal structure of macrophage migration inhibitory factor complexed with (E)-2-fluoro-p-hydroxycinnamate at 1.8 A resolution: implications for enzymatic catalysis and inhibition.
  Biochemistry, 38, 7444-7452.
PDB code: 1mfi
10353846 J.B.Lubetsky, M.Swope, C.Dealwis, P.Blake, and E.Lolis (1999).
Pro-1 of macrophage migration inhibitory factor functions as a catalytic base in the phenylpyruvate tautomerase activity.
  Biochemistry, 38, 7346-7354.
PDB codes: 1ca7 1cgq 1p1g
9920865 J.Matsunaga, D.Sinha, L.Pannell, C.Santis, F.Solano, G.J.Wistow, and V.J.Hearing (1999).
Enzyme activity of macrophage migration inhibitory factor toward oxidized catecholamines.
  J Biol Chem, 274, 3268-3271.  
10397792 T.A.Soares, D.S.Goodsell, J.M.Briggs, R.Ferreira, and A.J.Olson (1999).
Docking of 4-oxalocrotonate tautomerase substrates: implications for the catalytic mechanism.
  Biopolymers, 50, 319-328.  
10576686 X.Zhang, and R.Bucala (1999).
Inhibition of macrophage migration inhibitory factor (MIF) tautomerase activity by dopachrome analogs.
  Bioorg Med Chem Lett, 9, 3193-3198.  
9778344 A.B.Taylor, R.M.Czerwinski, W.H.Johnson, C.P.Whitman, and M.L.Hackert (1998).
Crystal structure of 4-oxalocrotonate tautomerase inactivated by 2-oxo-3-pentynoate at 2.4 A resolution: analysis and implications for the mechanism of inactivation and catalysis.
  Biochemistry, 37, 14692-14700.
PDB code: 1bjp
9649424 M.Swope, H.W.Sun, P.R.Blake, and E.Lolis (1998).
Direct link between cytokine activity and a catalytic site for macrophage migration inhibitory factor.
  EMBO J, 17, 3534-3541.  
9629239 R.Bucala (1998).
Neuroimmunomodulation by macrophage migration inhibitory factor (MIF).
  Ann N Y Acad Sci, 840, 74-82.  
9665726 S.L.Stamps, M.C.Fitzgerald, and C.P.Whitman (1998).
Characterization of the role of the amino-terminal proline in the enzymatic activity catalyzed by macrophage migration inhibitory factor.
  Biochemistry, 37, 10195-10202.  
  9573204 Z.He, and J.C.Spain (1998).
A novel 2-aminomuconate deaminase in the nitrobenzene degradation pathway of Pseudomonas pseudoalcaligenes JS45.
  J Bacteriol, 180, 2502-2506.  
9348662 C.L.Perrin, and J.B.Nielson (1997).
"Strong" hydrogen bonds in chemistry and biology.
  Annu Rev Phys Chem, 48, 511-544.  
8804825 A.G.Murzin (1996).
Structural classification of proteins: new superfamilies.
  Curr Opin Struct Biol, 6, 386-394.  
8547260 J.T.Stivers, C.Abeygunawardana, A.S.Mildvan, G.Hajipour, C.P.Whitman, and L.H.Chen (1996).
Catalytic role of the amino-terminal proline in 4-oxalocrotonate tautomerase: affinity labeling and heteronuclear NMR studies.
  Biochemistry, 35, 803-813.  
8547261 J.T.Stivers, C.Abeygunawardana, A.S.Mildvan, G.Hajipour, and C.P.Whitman (1996).
4-Oxalocrotonate tautomerase: pH dependence of catalysis and pKa values of active site residues.
  Biochemistry, 35, 814-823.  
8973173 J.T.Stivers, C.Abeygunawardana, and A.S.Mildvan (1996).
15N NMR relaxation studies of free and inhibitor-bound 4-oxalocrotonate tautomerase: backbone dynamics and entropy changes of an enzyme upon inhibitor binding.
  Biochemistry, 35, 16036-16047.  
  8845763 J.T.Stivers, C.Abeygunawardana, C.P.Whitman, and A.S.Mildvan (1996).
4-Oxalocrotonate tautomerase, a 41-kDa homohexamer: backbone and side-chain resonance assignments, solution secondary structure, and location of active site residues by heteronuclear NMR spectroscopy.
  Protein Sci, 5, 729-741.  
8692908 M.C.Fitzgerald, I.Chernushevich, K.G.Standing, C.P.Whitman, and S.B.Kent (1996).
Probing the oligomeric structure of an enzyme by electrospray ionization time-of-flight mass spectrometry.
  Proc Natl Acad Sci U S A, 93, 6851-6856.  
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.