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PDBsum entry 1yfm

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protein links
Lyase PDB id
1yfm
Jmol
Contents
Protein chain
450 a.a. *
* Residue conservation analysis
PDB id:
1yfm
Name: Lyase
Title: Recombinant yeast fumarase
Structure: Fumarase. Chain: a. Synonym: yfum. Engineered: yes. Mutation: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: fum1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.60Å     R-factor:   0.196     R-free:   0.315
Authors: T.M.Weaver,M.R.Lees,L.J.Banaszak
Key ref:
T.Weaver et al. (1998). Crystal structures of native and recombinant yeast fumarase. J Mol Biol, 280, 431-442. PubMed id: 9665847 DOI: 10.1006/jmbi.1998.1862
Date:
07-Jan-98     Release date:   08-Jul-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08417  (FUMH_YEAST) -  Fumarate hydratase, mitochondrial
Seq:
Struc:
488 a.a.
450 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.4.2.1.2  - Fumarate hydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Citric acid cycle
      Reaction: (S)-malate = fumarate + H2O
(S)-malate
= fumarate
+ H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   5 terms 
  Biological process     fumarate metabolic process   2 terms 
  Biochemical function     catalytic activity     3 terms  

 

 
    Added reference    
 
 
DOI no: 10.1006/jmbi.1998.1862 J Mol Biol 280:431-442 (1998)
PubMed id: 9665847  
 
 
Crystal structures of native and recombinant yeast fumarase.
T.Weaver, M.Lees, V.Zaitsev, I.Zaitseva, E.Duke, P.Lindley, S.McSweeny, A.Svensson, J.Keruchenko, I.Keruchenko, K.Gladilin, L.Banaszak.
 
  ABSTRACT  
 
Crystal structures for both native and recombinant forms of yeast fumarase from Saccharomyces cerevisiae have been completed to moderate resolution by two separate laboratories. The recombinant form was obtained by the construction of an expression plasmid for Escherichia coli. Despite a high level of amino acid sequence similarity, purification of the eukaryotic enzyme from the wild-type prokaryotic enzyme was feasible. The crystal structure of the native form, NY-fumarase, encompasses residues R22 through M484, while the recombinant form, RY-fumarase, consists of residues S27 through L485. Both crystal structures lack the N-terminal translocation segment. Each subunit of the homo-tetrameric protein has three domains. The active site is formed by segments from each of three polypeptide chains. The results of these studies on the eukaryotic proteins are unique, since the recombinant form was done in the absence of dicarboxylic acid and has an unoccupied active site. As a comparison, native fumarase was crystallized in the presence of the competitive inhibitor, meso-tartrate. Meso-tartrate occupies a position close to that of the bound citrate molecule found in the active site of the E. coli enzyme. This inhibitor participates in hydrogen bonding to an active-site water molecule. The independent determination of the two structures provides further evidence that an active-site water molecule may play an active role in the fumarase-catalyzed reaction.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. Non-functional active-site region of δ-crystallin. The stereo-diagram contains a representation of atoms in the crystal structure of δ-crystallin that are homologous to those in the active site of the Y-fumarases. Atoms are positioned in approximately the same orientation as the NY and RY-fumarase active sites illustrated by Figure 3(a) and (b). Labeling and color coding is the same as in Figure 3. The majority of the active-site residues of δ-crystallin are located in approximatley the same orientation as those in NY and RY-fumarase. However, I88 and T90, which represent the active-site residues S124 and T126 in NY and RY-fumarase, are shifted away from the active site and are no longer able to contribute hydrogen bonds to the active-site water molecule.
Figure 5.
Figure 5. A comparison of the activator sites from the crystal structures of NY and E-fumarase(c). The stereo-diagram illustrates the results of a superimposition of the crystallographic coordinates of NY-fumarase and E-fumarase(c) in the region of the second dicarboxylic acid binding site. The NY-fumarase positions are colored in violet, while those representing E-fumarase(c) are shaded in gold. The position of the activator, Image -malate, as found in the crystal structure of E-fumarase(c) is colored gray and is visible directly above the label H129.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 280, 431-442) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21243161 J.Jin, and U.Hanefeld (2011).
The selective addition of water to C=C bonds; enzymes are the best chemists.
  Chem Commun (Camb), 47, 2502-2510.  
17960613 A.Lorenzato, M.Olivero, M.Perro, J.J.Brière, P.Rustin, and M.F.Di Renzo (2008).
A cancer-predisposing "hot spot" mutation of the fumarase gene creates a dominant negative protein.
  Int J Cancer, 122, 947-951.  
17959599 A.Mukhopadhyay, C.S.Yang, B.Wei, and H.Weiner (2007).
Precursor Protein Is Readily Degraded in Mitochondrial Matrix Space if the Leader Is Not Processed by Mitochondrial Processing Peptidase.
  J Biol Chem, 282, 37266-37275.  
17666392 O.Yogev, S.Karniely, and O.Pines (2007).
Translation-coupled translocation of yeast fumarase into mitochondria in vivo.
  J Biol Chem, 282, 29222-29229.  
17054713 S.Halak, L.Lehtiö, T.Basta, S.Bürger, M.Contzen, A.Stolz, and A.Goldman (2006).
Structure and function of the 3-carboxy-cis,cis-muconate lactonizing enzyme from the protocatechuate degradative pathway of Agrobacterium radiobacter S2.
  FEBS J, 273, 5169-5182.
PDB codes: 2fel 2fen
16717409 T.Genda, S.Watabe, and H.Ozaki (2006).
Purification and characterization of fumarase from Corynebacterium glutamicum.
  Biosci Biotechnol Biochem, 70, 1102-1109.  
  16237213 N.A.Alam, S.Olpin, A.Rowan, D.Kelsell, I.M.Leigh, I.P.Tomlinson, and T.Weaver (2005).
Missense mutations in fumarate hydratase in multiple cutaneous and uterine leiomyomatosis and renal cell cancer.
  J Mol Diagn, 7, 437-443.  
12960177 E.Sass, S.Karniely, and O.Pines (2003).
Folding of fumarase during mitochondrial import determines its dual targeting in yeast.
  J Biol Chem, 278, 45109-45116.  
11846788 C.Schnarrenberger, and W.Martin (2002).
Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of higher plants. A case study of endosymbiotic gene transfer.
  Eur J Biochem, 269, 868-883.  
11698398 L.M.Sampaleanu, B.Yu, and P.L.Howell (2002).
Mutational analysis of duck delta 2 crystallin and the structure of an inactive mutant with bound substrate provide insight into the enzymatic mechanism of argininosuccinate lyase.
  J Biol Chem, 277, 4166-4175.
PDB code: 1k7w
  10739264 T.M.Weaver (2000).
The pi-helix translates structure into function.
  Protein Sci, 9, 201-206.  
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.