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PDBsum entry 5rla

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protein metals Protein-protein interface(s) links
Hydrolase PDB id
5rla
Jmol
Contents
Protein chains
314 a.a. *
Metals
_MN ×3
Waters ×46
* Residue conservation analysis
PDB id:
5rla
Name: Hydrolase
Title: Altering the binuclear manganese cluster of arginase diminishes thermostability and catalytic function
Structure: Arginase. Chain: a, b, c. Engineered: yes. Mutation: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Cell_line: bl21. Organ: liver. Cellular_location: cytoplasm. Gene: pargr-2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Homo-Trimer (from PDB file)
Resolution:
2.74Å     R-factor:   0.175     R-free:   0.270
Authors: L.R.Scolnick,Z.F.Kanyo,D.W.Christianson
Key ref:
L.R.Scolnick et al. (1997). Altering the binuclear manganese cluster of arginase diminishes thermostability and catalytic function. Biochemistry, 36, 10558-10565. PubMed id: 9265637 DOI: 10.1021/bi970800v
Date:
07-May-97     Release date:   13-May-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P07824  (ARGI1_RAT) -  Arginase-1
Seq:
Struc:
323 a.a.
314 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.3.5.3.1  - Arginase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Urea Cycle and Arginine Biosynthesis
      Reaction: L-arginine + H2O = L-ornithine + urea
L-arginine
+ H(2)O
= L-ornithine
+ urea
      Cofactor: Mn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   7 terms 
  Biological process     cellular response to lipopolysaccharide   35 terms 
  Biochemical function     hydrolase activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi970800v Biochemistry 36:10558-10565 (1997)
PubMed id: 9265637  
 
 
Altering the binuclear manganese cluster of arginase diminishes thermostability and catalytic function.
L.R.Scolnick, Z.F.Kanyo, R.C.Cavalli, D.E.Ash, D.W.Christianson.
 
  ABSTRACT  
 
Arginase is a thermostable (Tm = 75 degrees C) binuclear manganese metalloenzyme which hydrolyzes l-arginine to form l-ornithine and urea. The three-dimensional structures of native metal-depleted arginase, metal-loaded H101N arginase, and metal-depleted H101N arginase have been determined by X-ray crystallographic methods to probe the roles of the manganese ion in site A (Mn2+A) and its ligand H101 in catalysis and thermostability. We correlate these structures with thermal stability and catalytic activity measurements reported here and elsewhere [Cavalli, R. C., Burke, C. J., Kawamoto, S., Soprano, D. R., and Ash, D. E. (1994) Biochemistry 33, 10652-10657]. We conclude that the substitution of a wild-type histidine ligand to Mn2+A compromises metal binding, which in turn compromises protein thermostability and catalytic function. Therefore, a fully occupied binuclear manganese metal cluster is required for optimal catalysis and thermostability.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20512387 G.Colotti, and A.Ilari (2011).
Polyamine metabolism in Leishmania: from arginine to trypanothione.
  Amino Acids, 40, 269-285.  
  20050660 E.M.Stone, E.S.Glazer, L.Chantranupong, P.Cherukuri, R.M.Breece, D.L.Tierney, S.A.Curley, B.L.Iverson, and G.Georgiou (2010).
Replacing Mn(2+) with Co(2+) in human arginase i enhances cytotoxicity toward l-arginine auxotrophic cancer cell lines.
  ACS Chem Biol, 5, 333-342.  
21053939 E.M.Stone, L.Chantranupong, and G.Georgiou (2010).
The second-shell metal ligands of human arginase affect coordination of the nucleophile and substrate.
  Biochemistry, 49, 10582-10588.  
19456858 G.A.Wells, I.B.Müller, C.Wrenger, and A.I.Louw (2009).
The activity of Plasmodium falciparum arginase is mediated by a novel inter-monomer salt-bridge between Glu295-Arg404.
  FEBS J, 276, 3517-3530.  
19288480 M.Leopoldini, N.Russo, and M.Toscano (2009).
Determination of the catalytic pathway of a manganese arginase enzyme through density functional investigation.
  Chemistry, 15, 8026-8036.  
18488197 H.Kanda, D.Sumi, A.Endo, T.Toyama, C.L.Chen, M.Kikushima, and Y.Kumagai (2008).
Reduction of arginase I activity and manganese levels in the liver during exposure of rats to methylmercury: a possible mechanism.
  Arch Toxicol, 82, 803-808.  
16981206 L.Di Costanzo, L.V.Flores, and D.W.Christianson (2006).
Stereochemistry of guanidine-metal interactions: implications for L-arginine-metal interactions in protein structure and function.
  Proteins, 65, 637-642.  
15843155 I.B.Müller, R.D.Walter, and C.Wrenger (2005).
Structural metal dependency of the arginase from the human malaria parasite Plasmodium falciparum.
  Biol Chem, 386, 117-126.  
15375162 I.Benzaghou, I.Bougie, and M.Bisaillon (2004).
Effect of metal ion binding on the structural stability of the hepatitis C virus RNA polymerase.
  J Biol Chem, 279, 49755-49761.  
14705018 I.Ivanov, and M.L.Klein (2004).
First principles computational study of the active site of arginase.
  Proteins, 54, 1-7.  
11739398 H.C.Chang, W.Y.Chou, and G.G.Chang (2002).
Effect of metal binding on the structural stability of pigeon liver malic enzyme.
  J Biol Chem, 277, 4663-4671.  
10872443 D.W.Christianson, and J.D.Cox (1999).
Catalysis by metal-activated hydroxide in zinc and manganese metalloenzymes.
  Annu Rev Biochem, 68, 33-57.  
10353848 H.Teng, and C.Grubmeyer (1999).
Mutagenesis of histidinol dehydrogenase reveals roles for conserved histidine residues.
  Biochemistry, 38, 7363-7371.  
10387007 W.T.Lowther, A.M.Orville, D.T.Madden, S.Lim, D.H.Rich, and B.W.Matthews (1999).
Escherichia coli methionine aminopeptidase: implications of crystallographic analyses of the native, mutant, and inhibited enzymes for the mechanism of catalysis.
  Biochemistry, 38, 7678-7688.
PDB codes: 2mat 3mat 4mat
9520390 M.C.Wilce, C.S.Bond, N.E.Dixon, H.C.Freeman, J.M.Guss, P.E.Lilley, and J.A.Wilce (1998).
Structure and mechanism of a proline-specific aminopeptidase from Escherichia coli.
  Proc Natl Acad Sci U S A, 95, 3472-3477.
PDB codes: 1a16 1az9 1jaw
9548962 S.F.Martin, and P.J.Hergenrother (1998).
General base catalysis by the phosphatidylcholine-preferring phospholipase C from Bacillus cereus: the role of Glu4 and Asp55.
  Biochemistry, 37, 5755-5760.  
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.