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Zinc Peptidase

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    Tag pages as 'Zinc_Peptidase' to appear in this list.

    Name Annotation Author(s)
    3k2k
    Pfam update: This sequence matches Peptidase_M14 (PF00246). This is a putative zinc peptidase. The putative active site is at His171, His268 and Glu174 (red sticks). Other residues Glu344, Glu271 and... debanu (5 edits)
    3cpx
    This target belongs to the CATH family 3.40.630.10 of alpha-beta proteins and the zinc peptidase homologous superfamily. Analysis of molecular packing in the crystal structure indicates that the stru... kellrott (3 edits)
    debanu (1 edits)
    3fmc
     Gene Sama_0604 from Shewanella amazonensis SB2B encodes the YP_926482 protein that belongs to the AstE_AspA (Succinylglutamate desuccinylase / Aspartoacylase family) group PF04952 . This family inclu... gyewon (13 edits)
    pascual (2 edits)
    3lwu
    The protein YP_749235.1 is annotated as Succinylglutamate desuccinylase/aspartoacylase. YP_749235.1 belongs to PFAM PF04952 AstE_AspA which includes Succinylglutamate desuccinylase EC:3.1.-.- that cat... abhinavk (5 edits)
    kellrott (1 edits)
    3gux
    Member of Peptidase M28 family   Gene BVU_1317 from Bacteroides vulgatus translates into the YP_001298628 protein. NCBI blast sequence alignment suggests BVU_1317 is a leucine aminopeptidase precursor... pascual (3 edits)
    kevinjin (2 edits)
    chrisx (1 edits)
    375171
    2rb7
    YP_387682 is a co-catalytic metallopeptidase with significant structural (PDB: 1cg2, 2f7v, 2pok, 1vgy, 1fno, 1lfw, 1r3n, and 1xmb), and sequence similarity to zinc metallopeptidases (PF01546) and acet...
    3tx8
    This is a putative metallopeptidase and part of the zinc peptidase set of structures being solved. Additional information on these proteins can be found on the Topsan Zinc Peptidase site tagged below.... debanu (3 edits)
    4fuu
    Target ID 417178 is a member of the Peptidase_M28 (PF04389) Pfam family. This Pfam family is represented by over 113 structures in the PDB. A more detailed description from the Interpro database on th... haxelrod (6 edits)
    3pfe
    Pfam Update: This proetin is part of peptidease_M20 family which has known structures so this is not a high priority for us. This protein is annotated as succinyl-diaminopimelate desuccinylase belong... debanu (3 edits)
    haxelrod (1 edits)
    3isx
    This protein (TM1050) is annotated as an endoglucanase in Pfam PF05343 (Peptidase M42) which belongs to the Pfam clan CL0035 and CATH family of zinc metallopeptidases. For further analysis of this pro... debanu (3 edits)
    3gb0
    This protein is annotated as a peptidase. It belongs to the CATH family of zinc peptidases. It has two domains that are structurally conserved amongst similar proteins, the peptidase domain and the d... pkozbial (2 edits)
    debanu (1 edits)
    3ct9
    The protein is a dimer in the crystal structure and also in solution as seen by size-exclusion chormatography. There are two molecules/asu of the unit cell as show below. Each protomer has two domains... chrisx (1 edits)
    2qj8
    The mlr6093 gene (PF04952, cl11393, cd06252) from Mesorhizobium loti encodes for a putative succinylglutamate desuccinylase (EC:3.5.1.96), a metallocarboxypeptidase involved in the catabolism of argin... chrisx (12 edits)
    pascual (4 edits)
    3ieh
    Pfam update: This protein is now in family PF04952.7 AstE_AspA CL0035. Gene Sbal_3428 from Shewanella baltica os155 encodes the YP_001051774 protein, a putative zinc peptidase (CATH family 3.40.630.10... debanu (15 edits)
    pascual (3 edits)
    3l2n
    Pfam update: peptidate M14 family Gene Sden_1905 from S. denitrificans encodes a putative carboxypeptidase (YP_562911.1) belonging to the peptidase M14, Zn carboxypeptidase group PF00246. SCOP classif... pascual (5 edits)
    debanu (4 edits)
    3b2y
    Gene Sden_2526 from Shewanella denitrificans os-217 encodes the YP_563529 metallopeptidase containing a Ni metal in its putative active site. YP_563529.1 sequence belongs to the PF04952 family. SCOP ... pascual (5 edits)
    3iib
    Pfam update: This protein is now in families PF02225.15 PA, PF04389.10 Peptidase_M28 CL0035. This protein is present as a monomer in the asymmetric unit of the crystal structure, but the predicted ol... debanu (4 edits)
    3k9t
    This protein is annotated as an aminopeptidase domain contaning protein belonging to a new Pfam family of DUFs, DUF2172, PF09940. This family is comprised of 44 proteins from 41 species, mostly (33 o... debanu (3 edits)
    2qyv
     The HS_0004 gene (also known as pepD) gene (PF01546, cl09126) from Haemophilus somnus 129PT encodes for YP_718209, a zinc metallopeptidase (EC:3.4.13.3). More specifically, this protein is a M20C dip... chrisx (7 edits)
    pascual (3 edits)
    2fvg
    The TM1049 gene from Thermotoga maritima encodes an endoglucanase E.C.3.2.1.4 COG3405 PF05343.  The enzyme belongs to a family of FrvX endoglucanases (cellulase M and related proteins).  The enzyme ca... anton (2 edits)
    tinab (1 edits)

     

    Crystal structures of novel zinc proteases in Pfam clan CL0035 from recently sequenced bacterial genomes

                            (PDB accession codes listed above with links to their individual TOPSAN pages)

     N. B.:

    (1)A part of this work was presented as a poster at the International Union of Crystallography General Assemby in Osaka, Japan, in 2008 and at the Keystone meeting on Structural Genomics And Its Applications To Chemistry, Biology & Medicine in 2008.


    (2) See References, images, files, etc. tabs at end of this page

    (3) A total of 19 structures solved as per the latest count on 11/17/09, as listed above. These include mostly HP targets, 1 PX target, 1 GS target and 2 TM targets.

    Abstract

    In March 2007, the JCSG initiated a study of Proteins in the CATH family of Zinc Peptidases (CATH 3.40.630.10, phosphorylase/hydrolase-like fold in SCOP). These proteins have a broad phylogenetic spread across all kingdoms of life and show substantial sequence divergence. According to the latest Pfam v.24 (Oct 09), they are in 12 Pfam  families and form the large peptidase_MH/MC/MF clan CL0035. This Pfam clan includes a total of 23731 protein sequences from 1311 species. The unique 3D structures of a total of 77 out of these 23731 proteins (~3%) have been solved (449 structures in total).

    Methods and Target Selection

    JCSG improved the structural coverage by determining novel structures which share <30% sequence identity with those in the PDB. Hidden Markov Models from the CATH database were used to identify sequences in the JCSG genome pool. PSI-Blast seeded with these sequences was used to find additional proteins. These two sets yielded 226 unique targets. After removing targets with more than 30% sequence identity to any PDB structure or to any crystallized target from a structural genomics center, 161 targets remained. Further clustering at 90% (in order to avoid nearly identical sequences), produced a set of 137 targets. To date, JCSG has contributed 19 new structures to the family.

    Results

    We have analyzed features of these proteins that may support different functions, focusing on active sites, ligands, domain architectures and oligomerization. Even with a modest increase in structural coverage, we could assign new functional roles within the clan and more clearly discern the evolutionary connections in its PFAM families.

    We also identified many proteins of biomedical importance. Four structures can be used to model ~130 proteins in prevalent pathogenic bacteria and may allow the design of new therapies.

    Two carboxypeptidases (2rb7 and 3ct9) are close homologs of an enzyme that is used in prodrug and cancer therapy.

    Four AstE/AspA-like members (2qvp, 3b2y, 2qj8 and 3fmc) are bacterial homologs of a protein involved in a brain disease.

    We also obtained the first structure of an aminopeptidase with irons bound in the active site (3cpx), which hints at functional novelty.

    A putative Xaa-His dipeptidase represents the first structure of a PepD (2qyv) and reveals a dimeric form.

    One protein is from a human gut microbiome organism (3gux).

    One protein (3k9t) is from the new DUF2172 family that has been recently identified and annotated as belonging to this Pfam clan and is the first structure from this Pfam.

    Two structures from Pfam PF00246 (3k2k and 375163) show a novel N-terminal domain structure and the 375163 structure is also unique in binding Ca2+ in preference to Zn2+ in solution and the crystal structure has a Ca2+ at the active site.

     The following table provides an overview of the structural coverage within this Pfam clan and the structure determined by JCSG (need to update this table) and other SG (Structural Genomics) and non-SG groups.

    PF01520 Amidase_3 2725 proteins 0 JCSG 1 all other SG 2 non-SG  JCSG contribution  
    PF04952 AstE_AspA 1198 proteins 4 JCSG 7 all other SG 0 non-SG 36% coverag  only SG
    PF00246 PeptidaseM14 2256 proteins 2 JCSG 0 all other SG 15 non-SG 12% coverag  
    PF00883 PeptidaseM17 2117 proteins 0 JCSG 1 all other SG 2 non-SG    
    PF02127 PeptidaseM18 0701 proteins 0 JCSG 4 all other SG 0 non-SG    only SG
    PF01546 PeptidaseM20 10589 protei 4 JCSG 8 all other SG 8 non-SG 20% coverag  
    PF04389 PeptidaseM28 2357 proteins 2 JCSG 0 all other SG 6 non-SG 25% coverag  
    PF05343 PeptidaseM42 1260 proteins 2 JCSG 5 all other SG 2 non-SG 22% coverag  
    PF09940 DUF2172 0064 proteins 1 JCSG 0 all other SG 0 non-SG 100% covera  only SG
    PF10994 DUF2817 0061 proteins 0 JCSG 0 all other SG 0 non-SG    
    PF07454 SpoIIP 0307 proteins 0 JCSG 0 all other SG 0 non-SG    
    PF05450 Nicastrin 0096 proteins 0 JCSG 0 all other SG 0 non-SG    

     

    Reviews

    References

     

    No references found.

    Files (3)

    FileSizeDateAttached by 
     DD_HPFam_Analysis_Rev1_041008.xls
    Table of clustering and other features/properties of structures in this Pfam clan
    138 kB07:59, 9 May 2009debanuActions
     DD_IUCr_081208_2_42x42_iaw_testsize.pdf
    No description
    2.93 MB21:44, 5 Oct 2011debanuActions
     DD_KeySt_Final_010308_3_42x42.pdf
    No description
    3.22 MB21:43, 5 Oct 2011debanuActions
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