Limits...
Evolutionary history of tissue kallikreins.

Pavlopoulou A, Pampalakis G, Michalopoulos I, Sotiropoulou G - PLoS ONE (2010)

Bottom Line: The chromosomal co-localization in a single cluster distinguishes KLKs from trypsin and other trypsin-like proteases which are spread in different genetic loci.All the defining features of the KLKs were further found to be conserved in the novel KLK protein sequences.The study of this unique family will further assist in selecting new model organisms for functional studies of proteolytic pathways involving KLKs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, School of Health Sciences, University of Patras, Rion-Patras, Greece.

ABSTRACT
The gene family of human kallikrein-related peptidases (KLKs) encodes proteins with diverse and pleiotropic functions in normal physiology as well as in disease states. Currently, the most widely known KLK is KLK3 or prostate-specific antigen (PSA) that has applications in clinical diagnosis and monitoring of prostate cancer. The KLK gene family encompasses the largest contiguous cluster of serine proteases in humans which is not interrupted by non-KLK genes. This exceptional and unique characteristic of KLKs makes them ideal for evolutionary studies aiming to infer the direction and timing of gene duplication events. Previous studies on the evolution of KLKs were restricted to mammals and the emergence of KLKs was suggested about 150 million years ago (mya). In order to elucidate the evolutionary history of KLKs, we performed comprehensive phylogenetic analyses of KLK homologous proteins in multiple genomes including those that have been completed recently. Interestingly, we were able to identify novel reptilian, avian and amphibian KLK members which allowed us to trace the emergence of KLKs 330 mya. We suggest that a series of duplication and mutation events gave rise to the KLK gene family. The prominent feature of the KLK family is that it consists of tandemly and uninterruptedly arrayed genes in all species under investigation. The chromosomal co-localization in a single cluster distinguishes KLKs from trypsin and other trypsin-like proteases which are spread in different genetic loci. All the defining features of the KLKs were further found to be conserved in the novel KLK protein sequences. The study of this unique family will further assist in selecting new model organisms for functional studies of proteolytic pathways involving KLKs.

Show MeSH

Related in: MedlinePlus

A, Secondary structure prediction of putative KLKs.Sequences corresponding to the conserved trypsin domain were aligned using PROMALS3D. The residues of the catalytic triad are shown on the black background; the glycine residue is shown on the gray background. The consensus secondary structure is shown at the bottom, where the α-helices are represented by cylinders and the β-sheets by arrows. KLKs with known crystal structure were used as reference; their PDB accession codes are: KLK1(1spj), KLK5(2psy), KLK6 (1gvl). B, Tertiary structure of proKLK6. Graphic visualization of the human proKLK6 protein color coded by conservation score, where the region in blue corresponds to the most highly conserved region. KLK6 is represented as a cartoon. The four conserved amino acid residues (His 57, Asp102, Ser195 and Gly193) are indicated.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2967472&req=5

pone-0013781-g005: A, Secondary structure prediction of putative KLKs.Sequences corresponding to the conserved trypsin domain were aligned using PROMALS3D. The residues of the catalytic triad are shown on the black background; the glycine residue is shown on the gray background. The consensus secondary structure is shown at the bottom, where the α-helices are represented by cylinders and the β-sheets by arrows. KLKs with known crystal structure were used as reference; their PDB accession codes are: KLK1(1spj), KLK5(2psy), KLK6 (1gvl). B, Tertiary structure of proKLK6. Graphic visualization of the human proKLK6 protein color coded by conservation score, where the region in blue corresponds to the most highly conserved region. KLK6 is represented as a cartoon. The four conserved amino acid residues (His 57, Asp102, Ser195 and Gly193) are indicated.

Mentions: Furthermore, it is demonstrated that the novel KLK amino acid sequences possess the secondary structure of known KLKs [34]–[36] (Figure 5a). The degree of conservation of the four catalytically important amino acids is shown in the known three dimensional structure of human proKLK6 [34] (Figure 5b) where they appear to be located in the most conserved region which is the cleft between the two trypsin-like serine protease domains (thrombin, subunit H beta-barrels; CATH Code: 2.40.10.10).


Evolutionary history of tissue kallikreins.

Pavlopoulou A, Pampalakis G, Michalopoulos I, Sotiropoulou G - PLoS ONE (2010)

A, Secondary structure prediction of putative KLKs.Sequences corresponding to the conserved trypsin domain were aligned using PROMALS3D. The residues of the catalytic triad are shown on the black background; the glycine residue is shown on the gray background. The consensus secondary structure is shown at the bottom, where the α-helices are represented by cylinders and the β-sheets by arrows. KLKs with known crystal structure were used as reference; their PDB accession codes are: KLK1(1spj), KLK5(2psy), KLK6 (1gvl). B, Tertiary structure of proKLK6. Graphic visualization of the human proKLK6 protein color coded by conservation score, where the region in blue corresponds to the most highly conserved region. KLK6 is represented as a cartoon. The four conserved amino acid residues (His 57, Asp102, Ser195 and Gly193) are indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2967472&req=5

pone-0013781-g005: A, Secondary structure prediction of putative KLKs.Sequences corresponding to the conserved trypsin domain were aligned using PROMALS3D. The residues of the catalytic triad are shown on the black background; the glycine residue is shown on the gray background. The consensus secondary structure is shown at the bottom, where the α-helices are represented by cylinders and the β-sheets by arrows. KLKs with known crystal structure were used as reference; their PDB accession codes are: KLK1(1spj), KLK5(2psy), KLK6 (1gvl). B, Tertiary structure of proKLK6. Graphic visualization of the human proKLK6 protein color coded by conservation score, where the region in blue corresponds to the most highly conserved region. KLK6 is represented as a cartoon. The four conserved amino acid residues (His 57, Asp102, Ser195 and Gly193) are indicated.
Mentions: Furthermore, it is demonstrated that the novel KLK amino acid sequences possess the secondary structure of known KLKs [34]–[36] (Figure 5a). The degree of conservation of the four catalytically important amino acids is shown in the known three dimensional structure of human proKLK6 [34] (Figure 5b) where they appear to be located in the most conserved region which is the cleft between the two trypsin-like serine protease domains (thrombin, subunit H beta-barrels; CATH Code: 2.40.10.10).

Bottom Line: The chromosomal co-localization in a single cluster distinguishes KLKs from trypsin and other trypsin-like proteases which are spread in different genetic loci.All the defining features of the KLKs were further found to be conserved in the novel KLK protein sequences.The study of this unique family will further assist in selecting new model organisms for functional studies of proteolytic pathways involving KLKs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, School of Health Sciences, University of Patras, Rion-Patras, Greece.

ABSTRACT
The gene family of human kallikrein-related peptidases (KLKs) encodes proteins with diverse and pleiotropic functions in normal physiology as well as in disease states. Currently, the most widely known KLK is KLK3 or prostate-specific antigen (PSA) that has applications in clinical diagnosis and monitoring of prostate cancer. The KLK gene family encompasses the largest contiguous cluster of serine proteases in humans which is not interrupted by non-KLK genes. This exceptional and unique characteristic of KLKs makes them ideal for evolutionary studies aiming to infer the direction and timing of gene duplication events. Previous studies on the evolution of KLKs were restricted to mammals and the emergence of KLKs was suggested about 150 million years ago (mya). In order to elucidate the evolutionary history of KLKs, we performed comprehensive phylogenetic analyses of KLK homologous proteins in multiple genomes including those that have been completed recently. Interestingly, we were able to identify novel reptilian, avian and amphibian KLK members which allowed us to trace the emergence of KLKs 330 mya. We suggest that a series of duplication and mutation events gave rise to the KLK gene family. The prominent feature of the KLK family is that it consists of tandemly and uninterruptedly arrayed genes in all species under investigation. The chromosomal co-localization in a single cluster distinguishes KLKs from trypsin and other trypsin-like proteases which are spread in different genetic loci. All the defining features of the KLKs were further found to be conserved in the novel KLK protein sequences. The study of this unique family will further assist in selecting new model organisms for functional studies of proteolytic pathways involving KLKs.

Show MeSH
Related in: MedlinePlus