PDBsum entry: 1y7o

Hydrolase

PDB id: 1y7o

Contents

Protein chains

171 a.a. *

(+ 0 more) 178 a.a. *

Metals

_CA ×8

Waters ×144

* Residue conservation analysis

PDB id:

1y7o

Name:

Hydrolase

Title:

The structure of streptococcus pneumoniae a153p clpp

Structure:

Atp-dependent clp protease proteolytic subunit. Chain: a, b, c, d, e, f, g. Fragment: caseinolytic protease. Synonym: endopeptidase clp. Engineered: yes. Mutation: yes

Source:

Streptococcus pneumoniae. Organism_taxid: 1313. Gene: clpp. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Heptamer (from PDB file)

Resolution:

2.51Å R-factor: 0.192 R-free: 0.248

Authors:

M.S.Kimber,A.Gribun,R.Ching,R.Sprangers,K.M.Fiebig,W.A.Houry

Key ref:

A.Gribun et al. (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. PubMed id: 15701650 DOI: 10.1074/jbc.M414124200

Date:

09-Dec-04 Release date: 08-Feb-05

Protein chain

P63788  (CLPP_STRR6) -  ATP-dependent Clp protease proteolytic subunit

Seq: 196 a.a.

Struc: 171 a.a.*

Protein chains

P63788  (CLPP_STRR6) -  ATP-dependent Clp protease proteolytic subunit

Seq: 196 a.a.

Struc: 178 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F, G: E.C.3.4.21.92 - Endopeptidase Clp.
• 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 

• Cellular component: cytoplasm (1 term)
• Biological process: proteolysis (1 term)
• Biochemical function: nucleotide binding (6 terms)

DOI no: 10.1074/jbc.M414124200

J Biol Chem 280:16185-16196 (2005)

PubMed id: 15701650

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.

A.Gribun, M.S.Kimber, R.Ching, R.Sprangers, K.M.Fiebig, W.A.Houry.

ABSTRACT

ClpP is a conserved serine-protease with two heptameric rings that enclose a large chamber containing the protease active sites. Each ClpP subunit can be divided into a handle region, which mediates ring-ring interactions, and a head domain. ClpP associates with the hexameric ATPases ClpX and ClpA, which can unfold and translocate substrate proteins through the ClpP axial pores into the protease lumen for degradation. We have determined the x-ray structure of Streptococcus pneumoniae ClpP(A153P) at 2.5 A resolution. The structure revealed two novel features of ClpP which are essential for ClpXP and ClpAP functional activities. First, the Ala --> Pro mutation disrupts the handle region, resulting in an altered ring-ring dimerization interface, which, in conjunction with biochemical data, demonstrates the unusual plasticity of this region. Second, the structure shows the existence of a flexible N-terminal loop in each ClpP subunit. The loops line the axial pores in the ClpP tetradecamer and then protrude from the protease apical surface. The sequence of the N-terminal loop is highly conserved in ClpP across all kingdoms of life. These loops are essential determinants for complex formation between ClpP and ClpX/ClpA. Mutation of several amino acid residues in this loop or the truncation of the loop impairs ClpXP and ClpAP complex formation and prevents the coupling between ClpX/ClpA and ClpP activities.

Selected figure(s)

Figure 1.
FIG. 1. Alignment of S. pneumoniae and E. coli ClpP sequences. The alignment is based on the Blosum62 matrix used in ClustalW. Identical residues in the two sequences are in orange; very similar residues are in blue. Residues in the catalytic triad are indicated by red asterisks, and Ala^153 is indicated by a green asterisk. The axial loop and the handle region are boxed. The numbering of the helices and strands is the same as that of Wang et al. (21).

Figure 5.
FIG. 5. Structure of the N-terminal axial loops. A, A-weighted 2F[o] - F[c] electron density at 1 in the N-terminal loop region of chain D. Carbon atoms are colored differently for different chains. B, top view of the SpClpP(A153P) tetra-decamer showing backbone and transparent surfaces looking down the 7-fold axis. The N-terminal loop of each monomer is colored differently, and the rest of the molecule is shown in white. In contrast to the rest of the ring, the axial pore is quite asymmetric. C, detail of a representative N-terminal axial loop looking across the pore. Residues 16-32 of chain D are drawn in stick representation, whereas the rest of the structure is drawn in cartoon representation. The 7-fold symmetry axis is oriented vertically. Residues are labeled in accordance with the SwissProt EcClpP numbering. D, overlay of the N-terminal loops of seven monomers from one ring in the asymmetric unit of the SpClpP(A153P) crystal. Five monomers that resemble the conformer in B are shown in white; the two monomers shown in green and cyan deviate markedly from this consensus, being partially displaced into the pore. E, structure of residues 25-32 in EcClpP (21). Residues 31-32 form a -turn, whereas residues N-terminal to Ser25 are not resolved.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 16185-16196) copyright 2005.

Figures were selected by an automated process.