On the basis of sequence and structure similarity heme-dependent peroxidases can be separated into two families, the family or animal peroxidases and the family of plant, fungal, and bacterial peroxidases. The SCOP database puts the animal peroxidases under the family: myeloperoxidase-like. This family has two species whose structures are deposited in PDB, myeloperoxidase (found humans and dogs), and prostaglandin H2 synthase (found in sheep and mice).
SCOP classifies the plant, fungal, and bacterial peroxidases under the Cytochrome-C Peroxidase like family. This family has 6 species under it: Peanut Peroxidase(PDB ID: 1sch) and Horseradish Peroxidase(1atj), Yeast Cytochrome-C Peroxidase(2cyp), Lignin Peroxidase from White Rot Basidiomycete(1b82), Arthromyces Ramous Peroxidase(1arp), Peroxidase from Barley(1bgp), and Manganese Peroxidase from Basidiomycetos Fungus(1mnp).
It useful to look at the sequence alignment of the different peroxidase species mentioned. A map of conserved amino acid residues over the different species is vital in studying protein evolution.
Most often, however, three dimensional structure is more conserved than sequences. A comparison of strutures would be useful in providing information on common origins, function conservation, and conserved structural features that are important for the family which the protein belongs to.
A number of databases offer sequence alignment, structure alignment, and even both. Among these are DALI/FSSP, SAS - Sequences Annotated by Structure, and 3dSearch - Secondary Structure Superposition.
The SAS or Sequences Annotated by Structure website generates a structural alignment of protein chains using the FASTA algorithm from a PDB ID code input. For a structural alignment of HRP (PDB ID = 1atj) with similar sequences in the Protein Data Bank using FASTA click here (this list was created by the SAS server). After generating a sequence alignment, a 3D view or a structure superposition of selected sequences is offered. Some examples are the following (note: only monomer chains are aligned; the monomer chains are shown as cartoon representations):
HRP and Barley Grain Peroxidase
HRP and Cytochrome-C Peroxidase
HRP, Peanut Peroxidase, and Ascorbate Peroxidase
HRP, Peanut Peroxidase, Barley Grain Peroxidase, Ascorbate Peroxidase, and Cytochrome-C Peroxidase
The FSSP database is a classification database based on sequence-structure alignment done by the database's DALI server. A user can send a sequence to the DALI server and ask for it to align the sequence with a specific sequence in PDB or generate a list of alignments with respect to files available in the Protein Data Bank. Entering a PDB ID code into the DALI Server generates a list of similar sequences aligned by DALI. Click here to view a sample list. Like SAS, there is an option to view in 3D aligned PDB structure files selected by the user. Sample DALI sequence and structure alignments are:
Sequence Alignment: HRP and Barley Grain Peroxidase
Structure Alignment: HRP and Barley Grain Peroxidase
Another website which offers alignment is 3dSearch. The algorithm this website uses is a secondary structure superposition algorithm. A user can choose between single pair alignment or multiple pair alignment. The output is an aligned list of secondary structures of each PDB structure file. A 3D view of the aligned secondary structures is offered:
Secondary Structure List:
HRP (1atj) aligned with -
3D Superimposition of Secondary Structures:
HRP with Barley Grain Peroxidase (1bgp)
HRP with Human Myeloperoxidase (1mhl)
HRP with Arthromyces Ramous Peroxidase (1arp)
HRP with Manganese Peroxidase (1mnp)
HRP with Peanut Peroxidase (1sch)
HRP with Cytochrome-C Peroxidase (2cyp)
Among all the secondary structural alignments above, the most number of SS HRP aligned with are Peanut Peroxidase and Barley Grain Peroxidase. Evidently, these three have a common evolutionary origin. This can also be seen in CATH and SCOP. The least number of alignments is the alignment between HRP and Human Myeloperoxidase. This shows that indeed, animal and plant peroxidases, although similar in function, have different structural characteristics.
Clearly, the sequence and structure alignments show that these Peroxidases are very much related and have a common evolutionary origin. Alignments such as these are the basis for classification databases such as SCOP, CATH, and FSSP. Common structural characteristics from the alignments and the databases mentioned have been summarized in the Structure section.