3qkb

Protein Summary

Protein PEPE_0654 (JCSG target ID 392698, JCSG target accession code FR14867A, GenBank accession code YP_804159.1) is a 92-residue long protein from Pediococcus pentosaceus atcc 25745, a Gram-positive, coccus-shaped bacteria that is known as a “lactic acid bacteria” because lactic acid is the end product of its metabolism.  Biotechnology applications of the microbe include the fermentation and preservation of foods. Close homologs of PEPE_0654 are found in other Lactibacilli, but more distant ones are found across all bacteria, where they usually are present as a single homolog. 

PEPE_0654 belongs to Pfam DUF74 (PF01906),  a very large (~1000) member family of ~100-residue long domains of unknown function (DUF) that are found in prokaryotes, but also in pathogenic fungi and protists.  The structure of PEPE_0654 represents the third one from this family, with others being solved by other PSI centers and annotated as hypothetical proteins.  If the threshold in a Pfam search is reduced, PEPE_0654 is also found to belong to Pfam PF11524, which is a family of selenium binding proteins.

Genome context analysis by STRING suggests that functional partners of PEPE_0654 may include a putative hydrolase of the haloacid dehalogenase (HAD) superfamily (PEPE_0651) and a deoxynucleoside kinase (PEPE_0650).

The structure of PEPE_0654 was determined by the Se-Met MAD method to a resolution of 2.73 Angstroms.  The fold of a monomer of PEPE_0654 consists of an alpha-helix and a 3-stranded beta-sheet (Figure 1) and belongs to the YbjQ-like superfamily in the SCOP classification scheme. 

Structural classification and structure similarity analysis (see below) of PEPE_0654 confirms the distant homology to PFAM family of selenium binding proteins (PF11524) seen by FFAS and HHpred. It is interesting to note that other proteins from the same SCOP fold, sharing some distant sequence and strong structural similarities, include copper binding domain of the Alzheimer's disease amyloid precursor protein.  Heavy metal binding and complex formation (see below) seem to be two common themes in the extended family of PEPE_0654.

Figure 1.  Structure of a monomer of PEPE_0654 (a) gradiently colored from the N- (blue) to the C-terminus (red).

The structure of PEPE_0654 contains 5 molecules per asymmetric unit which form a pentamer (Figure 2ab).  This pentameric oligomeric state of PEPE_0654 is adopted by other members of the YbjQ-like superfamily and is also supported by PISA analysis.

Figure 2.  Orthogonal views of the structure of a pentamer of PEPE_0654.  (b) is rotated 90 degrees about the horizontal axis from (a).

(a)                                                                                            (b)

A structural neighbor search with DALI results in the top hits being hypothetical proteins APC22750 and BC_1816 from Bacillus cereus (PDB IDs 1vr4 and 2gtc), hypothetical protein S0862 from Shigella flexneri (PDB ID 1y2i), and a selenium-binding protein from Methanococcus vannielii (PDB ID 2jz7) (Table 1).

Table 1.   Top structural neighbors of PEPE_0654 as assessed by DALI.  Proteins which have been superimposed with PEPE_0654 are color-highlighted (see Figure 3).

The fold exhibited by these structural neighbors is very similar to that of PEPE_0654.  Moreover, like PEPE_0654, the closest structural neighbors are also pentamers (Figure 3), while more distant ones form decamers (2vxa), hexamers (2dev), or dimers (1xrs, 2c35 - not recognized by DALI search, since these are domains in large, multidomain proteins). 

Figure 3.  Superposition of PEPE_0654 (yellow) with top 4 DALI structural neighbors: PDB ids 1vr4 (blue), 2gtc (red), 1y2i (green), and 2jz7 (purple).

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Ligand Summary