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PDBsum entry 1lus

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protein metals Protein-protein interface(s) links
Oxidoreductase PDB id
1lus
Jmol
Contents
Protein chains
198 a.a.
Metals
_MN ×2
Waters ×290
Superseded by: 1n0n 1n0n
PDB id:
1lus
Name: Oxidoreductase
Title: Catalytic and structural effects of amino-acid substitution at his 30 in human mnsod: insertion of val cgamma into the substrate access channel
Structure: Superoxide dismutase [mn]. Chain: a, b. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Expressed in: escherichia coli.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.11Å     R-factor:   0.242     R-free:   0.276
Authors: A.S.Hearn,M.E.Stroupe,C.Ramilo,J.P.Luba,D.E.Cabelli, J.A.Tainer,H.S.Nick,D.N.Silverman
Key ref:
A.S.Hearn et al. (2003). Catalytic and structural effects of amino acid substitution at histidine 30 in human manganese superoxide dismutase: insertion of valine C gamma into the substrate access channel. Biochemistry, 42, 2781-2789. PubMed id: 12627943 DOI: 10.1021/bi0266481
Date:
23-May-02     Release date:   19-Jun-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P04179  (SODM_HUMAN) -  Superoxide dismutase [Mn], mitochondrial
Seq:
Struc:
222 a.a.
198 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.1.15.1.1  - Superoxide dismutase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2 superoxide + 2 H+ = O2 + H2O2
2 × superoxide
+ 2 × H(+)
= O(2)
+ H(2)O(2)
      Cofactor: Fe cation or Mn(2+) or (Zn(2+) and Cu cation)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1021/bi0266481 Biochemistry 42:2781-2789 (2003)
PubMed id: 12627943  
 
 
Catalytic and structural effects of amino acid substitution at histidine 30 in human manganese superoxide dismutase: insertion of valine C gamma into the substrate access channel.
A.S.Hearn, M.E.Stroupe, D.E.Cabelli, C.A.Ramilo, J.P.Luba, J.A.Tainer, H.S.Nick, D.N.Silverman.
 
  ABSTRACT  
 
Catalysis of the disproportionation of superoxide by human manganese superoxide dismutase (MnSOD) is characterized by an initial burst of catalysis followed by a much slower region that is zero order in superoxide and due to a product inhibition by peroxide anion. We have prepared site-specific mutants with replacements at His30, the side chain of which lies along the substrate access channel and is about 5.8 A from the metal. Using pulse radiolysis to generate superoxide, we have determined that kcat/K(m) was decreased and product inhibition increased for H30V MnSOD, both by 1-2 orders of magnitude, compared with wild type, H30N, and H30Q MnSOD. These effects are not attributed to the redox potentials, which are similar for all of these variants. An investigation of the crystal structure of H30V Mn(III)SOD compared with wild type, H30Q, and H30N Mn(III)SOD showed the positions of two gamma carbons of Val30 in the active site; Cgamma1 overlaps Cgamma of His30 in wild type, and Cgamma2 extends into the substrate access channel and occupies the approximate position of a water molecule in the wild type. The data suggest that Cgamma2 of the Val side chain has significantly interrupted catalysis by this overlap into the access channel with possible overlap with the substrate-product binding site. This is supported by comparison of the crystal structure of H30V MnSOD with that of azide bound to Mn(III)SOD from Thermus thermophilus and by visible absorption spectra showing that azide binding to the metal in H30V Mn(III)SOD is abolished. Moreover, the presence of Val30 caused a 100-fold decrease in the rate constant for dissociation of the product-inhibited complex compared with wild type.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19018482 C.Dong, G.Li, Z.Li, H.Zhu, M.Zhou, and Z.Hu (2009).
Molecular cloning and expression analysis of an Mn-SOD gene from Nelumbo nucifera.
  Appl Biochem Biotechnol, 158, 605-614.  
19812362 J.A.Moreno, E.C.Yeomans, K.M.Streifel, B.L.Brattin, R.J.Taylor, and R.B.Tjalkens (2009).
Age-dependent susceptibility to manganese-induced neurological dysfunction.
  Toxicol Sci, 112, 394-404.  
19812365 J.A.Moreno, K.M.Streifel, K.A.Sullivan, M.E.Legare, and R.B.Tjalkens (2009).
Developmental exposure to manganese increases adult susceptibility to inflammatory activation of glia and neuronal protein nitration.
  Toxicol Sci, 112, 405-415.  
19657747 M.Aschner, K.M.Erikson, E.H.Hernández, and R.Tjalkens (2009).
Manganese and its role in Parkinson's disease: from transport to neuropathology.
  Neuromolecular Med, 11, 252-266.  
  19052361 C.H.Trinh, T.Hunter, E.E.Stewart, S.E.Phillips, and G.J.Hunter (2008).
Purification, crystallization and X-ray structures of the two manganese superoxide dismutases from Caenorhabditis elegans.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1110-1114.
PDB codes: 3dc5 3dc6
18690655 M.Schmidt, S.Zahn, M.Carella, O.Ohlenschläger, M.Görlach, E.Kothe, and J.Weston (2008).
Solution structure of a functional biomimetic and mechanistic implications for nickel superoxide dismutases.
  Chembiochem, 9, 2135-2146.  
17912757 R.Wintjens, D.Gilis, and M.Rooman (2008).
Mn/Fe superoxide dismutase interaction fingerprints and prediction of oligomerization and metal cofactor from sequence.
  Proteins, 70, 1564-1577.  
17150313 B.Dash, R.Metz, H.J.Huebner, W.Porter, and T.D.Phillips (2007).
Molecular characterization of two superoxide dismutases from Hydra vulgaris.
  Gene, 387, 93.  
17174478 J.J.Perry, L.Fan, and J.A.Tainer (2007).
Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair.
  Neuroscience, 145, 1280-1299.  
16150974 I.Ayala, J.J.Perry, J.Szczepanski, J.A.Tainer, M.T.Vala, H.S.Nick, and D.N.Silverman (2005).
Hydrogen bonding in human manganese superoxide dismutase containing 3-fluorotyrosine.
  Biophys J, 89, 4171-4179.
PDB codes: 1xdc 1xil
15062777 A.F.Miller (2004).
Superoxide dismutases: active sites that save, but a protein that kills.
  Curr Opin Chem Biol, 8, 162-168.  
14638684 A.S.Hearn, L.Fan, J.R.Lepock, J.P.Luba, W.B.Greenleaf, D.E.Cabelli, J.A.Tainer, H.S.Nick, and D.N.Silverman (2004).
Amino acid substitution at the dimeric interface of human manganese superoxide dismutase.
  J Biol Chem, 279, 5861-5866.
PDB codes: 1pl4 1pm9
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.