4A39

Metallo-carboxypeptidase from Pseudomonas Aeruginosa in complex with (2-guanidinoethylmercapto)succinic acid

Summary for 4A39

• Entry DOI: 10.2210/pdb4a39/pdb
• Related: 4A37 4A38
• Descriptor: METALLO-CARBOXYPEPTIDASE, ZINC ION, (2-GUANIDINOETHYLMERCAPTO)SUCCINIC ACID, ... (4 entities in total)
• Functional Keywords: metallo-peptidase, hydrolase
• Biological source: PSEUDOMONAS AERUGINOSA
• Total number of polymer chains: 2
• Total formula weight: 89263.28

Authors

Otero, A.,Rodriguez de la Vega, M.,Tanco, S.M.,Lorenzo, J.,Aviles, F.X.,Reverter, D. (deposition date: 2011-09-30, release date: 2012-05-09, Last modification date: 2024-05-08)

Primary citation

Otero, A.,Rodriguez De La Vega, M.,Tanco, S.M.,Lorenzo, J.,Aviles, F.X.,Reverter, D.
The Novel Structure of a Cytosolic M14 Metallocarboxypeptidase (Ccp) from Pseudomonas Aeruginosa: A Model for Mammalian Ccps.
Faseb J., 26:3754-, 2012

PubMed Abstract: PaCCP is a metallocarboxypeptidase (MCP) of the M14 family from Pseudomonas aeruginosa, which belongs to a bacterial clade of carboxypeptidases that are homologous to the recently discovered M14D subfamily of human nonsecretory cytosolic carboxypeptidases (CCPs). CCPs are intracellular peptidases involved, among other roles, in the post-translational modifications of tubulin. Here we report the crystal structure of PaCCP at high resolution (1.6 Å). Its 375 residues are folded in a novel β-sandwich N-terminal domain followed by the classical carboxypeptidase α/β-hydrolase domain, this one in a shorter and more compact form. The former is unique in the whole family and does not have sequential or structural homology with other domains that are usually flanking the latter, like the prodomain of the M14A subfamily or the C-terminal transthyretin/prealbumin-like domains of the M14B subfamily. PaCCP does not display activity against small carboxypeptidase substrates, so in this form it might constitute an inactive precursor of the protease. Structural results derived from cocrystallization with well-known inhibitors of MCPs indicate that the enzyme might only possess C-terminal hydrolase activity against cellular substrates of particular specificity and/or when undergoes structural rearrangements. The derived PaCCP structure allows a first structural insight into the more complex and largely unknown mammalian CCP subfamily.

PubMed: 22645247
DOI: 10.1096/FJ.12-209601

Experimental method

X-RAY DIFFRACTION (1.6 Å)