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Hydrolase PDB id
1tg6
Jmol
Contents
Protein chains
184 a.a. *
196 a.a. *
Ligands
DIO ×6
EDO ×8
GOL ×6
FME ×7
Waters ×773
* Residue conservation analysis
PDB id:
1tg6
Name: Hydrolase
Title: Crystallography and mutagenesis point to an essential role f terminus of human mitochondrial clpp
Structure: Putative atp-dependent clp protease proteolytic s chain: a, b, c, d, e, f, g. Synonym: endopeptidase clp. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: clpp. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: 40mer (from PQS)
Resolution:
2.10Å     R-factor:   0.224     R-free:   0.262
Authors: S.G.Kang,M.R.Maurizi,M.Thompson,T.Mueser,B.Ahvazi
Key ref: S.G.Kang et al. (2004). Crystallography and mutagenesis point to an essential role for the N-terminus of human mitochondrial ClpP. J Struct Biol, 148, 338-352. PubMed id: 15522782 DOI: 10.1016/j.jsb.2004.07.004
Date:
28-May-04     Release date:   22-Mar-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q16740  (CLPP_HUMAN) -  Putative ATP-dependent Clp protease proteolytic subunit, mitochondrial
Seq:
Struc: 		277 a.a.
184 a.a.
Protein chains
Pfam   ArchSchema ?
Q16740  (CLPP_HUMAN) -  Putative ATP-dependent Clp protease proteolytic subunit, mitochondrial
Seq:
Struc: 		277 a.a.
196 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E, F, G: E.C.3.4.21.92  - Endopeptidase Clp.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of proteins to small peptides in the presence of ATP and magnesium. Alpha-casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are cleaved (such as succinyl-Leu-Tyr-|-NHMEC; and Leu-Tyr-Leu-|-Tyr-Trp, in which the cleavage of the -Tyr-|-Leu- and -Tyr-|-Trp- bond also occurs).
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrion   2 terms 
  Biological process     proteolysis   1 term 
  Biochemical function     nucleotide binding     7 terms  

 

 
DOI no: 10.1016/j.jsb.2004.07.004 J Struct Biol 148:338-352 (2004)
PubMed id: 15522782  
 
 
Crystallography and mutagenesis point to an essential role for the N-terminus of human mitochondrial ClpP.
S.G.Kang, M.R.Maurizi, M.Thompson, T.Mueser, B.Ahvazi.
 
  ABSTRACT  
 
We have determined a 2.1 A crystal structure for human mitochondrial ClpP (hClpP), the proteolytic component of the ATP-dependent ClpXP protease. HClpP has a structure similar to that of the bacterial enzyme, with the proteolytic active sites sequestered within an aqueous chamber formed by face-to-face assembly of the two heptameric rings. The hydrophobic N-terminal peptides of the subunits are bound within the narrow (12 A) axial channel, positioned to interact with unfolded substrates translocated there by the associated ClpX chaperone. Mutation or deletion of these residues causes a drastic decrease in ClpX-mediated protein and peptide degradation. Residues 8-16 form a mobile loop that extends above the ring surface and is also required for activity. The 28 amino acid C-terminal domain, a unique feature of mammalian ClpP proteins, lies on the periphery of the ring, with its proximal portion forming a loop that extends out from the ring surface. Residues at the start of the C-terminal domain impinge on subunit interfaces within the ring and affect heptamer assembly and stability. We propose that the N-terminal peptide of ClpP is a structural component of the substrate translocation channel and may play an important functional role as well.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20305655 B.G.Lee, E.Y.Park, K.E.Lee, H.Jeon, K.H.Sung, H.Paulsen, H.Rübsamen-Schaeff, H.Brötz-Oesterhelt, and H.K.Song (2010).
Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism.
  Nat Struct Mol Biol, 17, 471-478.
PDB codes: 3ktg 3kth 3kti 3ktj 3ktk
20851345 D.H.Li, Y.S.Chung, M.Gloyd, E.Joseph, R.Ghirlando, G.D.Wright, Y.Q.Cheng, M.R.Maurizi, A.Guarné, and J.Ortega (2010).
Acyldepsipeptide antibiotics induce the formation of a structured axial channel in ClpP: A model for the ClpX/ClpA-bound state of ClpP.
  Chem Biol, 17, 959-969.
PDB code: 3mt6
20637416 M.S.Kimber, A.Y.Yu, M.Borg, E.Leung, H.S.Chan, and W.A.Houry (2010).
Structural and theoretical studies indicate that the cylindrical protease ClpP samples extended and compact conformations.
  Structure, 18, 798-808.
PDB code: 3hln
19237538 F.I.Andersson, A.Tryggvesson, M.Sharon, A.V.Diemand, M.Classen, C.Best, R.Schmidt, J.Schelin, T.M.Stanne, B.Bukau, C.V.Robinson, S.Witt, A.Mogk, and A.K.Clarke (2009).
Structure and Function of a Novel Type of ATP-dependent Clp Protease.
  J Biol Chem, 284, 13519-13532.  
18816064 L.D.Jennings, J.Bohon, M.R.Chance, and S.Licht (2008).
The ClpP N-terminus coordinates substrate access with protease active site reactivity.
  Biochemistry, 47, 11031-11040.  
17612489 A.Martin, T.A.Baker, and R.T.Sauer (2007).
Distinct static and dynamic interactions control ATPase-peptidase communication in a AAA+ protease.
  Mol Cell, 27, 41-52.  
17242518 H.Ingvarsson, M.J.Maté, M.Högbom, D.Portnoï, N.Benaroudj, P.M.Alzari, M.Ortiz-Lombardía, and T.Unge (2007).
Insights into the inter-ring plasticity of caseinolytic proteases from the X-ray structure of Mycobacterium tuberculosis ClpP1.
  Acta Crystallogr D Biol Crystallogr, 63, 249-259.
PDB codes: 2c8t 2cby 2ce3
16705403 B.Zheng, T.M.MacDonald, S.Sutinen, V.Hurry, and A.K.Clarke (2006).
A nuclear-encoded ClpP subunit of the chloroplast ATP-dependent Clp protease is essential for early development in Arabidopsis thaliana.
  Planta, 224, 1103-1115.  
16877706 T.V.Rotanova, I.Botos, E.E.Melnikov, F.Rasulova, A.Gustchina, M.R.Maurizi, and A.Wlodawer (2006).
Slicing a protease: structural features of the ATP-dependent Lon proteases gleaned from investigations of isolated domains.
  Protein Sci, 15, 1815-1828.  
15701650 A.Gribun, M.S.Kimber, R.Ching, R.Sprangers, K.M.Fiebig, and W.A.Houry (2005).
The ClpP double ring tetradecameric protease exhibits plastic ring-ring interactions, and the N termini of its subunits form flexible loops that are essential for ClpXP and ClpAP complex formation.
  J Biol Chem, 280, 16185-16196.
PDB code: 1y7o
16263929 R.Sprangers, A.Gribun, P.M.Hwang, W.A.Houry, and L.E.Kay (2005).
Quantitative NMR spectroscopy of supramolecular complexes: dynamic side pores in ClpP are important for product release.
  Proc Natl Acad Sci U S A, 102, 16678-16683.  
16115876 S.G.Kang, M.N.Dimitrova, J.Ortega, A.Ginsburg, and M.R.Maurizi (2005).
Human mitochondrial ClpP is a stable heptamer that assembles into a tetradecamer in the presence of ClpX.
  J Biol Chem, 280, 35424-35432.  
16262695 W.Majeran, G.Friso, K.J.van Wijk, and O.Vallon (2005).
The chloroplast ClpP complex in Chlamydomonas reinhardtii contains an unusual high molecular mass subunit with a large apical domain.
  FEBS J, 272, 5558-5571.  
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.