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Analysis of proteins with the 'hot dog' fold: prediction of function and identification of catalytic residues of hypothetical proteins.

Pidugu LS, Maity K, Ramaswamy K, Surolia N, Suguna K - BMC Struct. Biol. (2009)

Bottom Line: The hot dog fold has been found in more than sixty proteins since the first report of its existence about a decade ago.This study reveals that though the basic architecture of the fold is well conserved in these proteins, significant differences exist in their sequence, nature of substrate and oligomerization.The analysis led to predictions regarding the functional classification and identification of possible catalytic residues of a number of hot dog fold-containing hypothetical proteins whose structures were determined in high throughput structural genomics projects.

View Article: PubMed Central - HTML - PubMed

Affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India. plsmukhi@gmail.com

ABSTRACT

Background: The hot dog fold has been found in more than sixty proteins since the first report of its existence about a decade ago. The fold appears to have a strong association with fatty acid biosynthesis, its regulation and metabolism, as the proteins with this fold are predominantly coenzyme A-binding enzymes with a variety of substrates located at their active sites.

Results: We have analyzed the structural features and sequences of proteins having the hot dog fold. This study reveals that though the basic architecture of the fold is well conserved in these proteins, significant differences exist in their sequence, nature of substrate and oligomerization. Segments with certain conserved sequence motifs seem to play crucial structural and functional roles in various classes of these proteins.

Conclusion: The analysis led to predictions regarding the functional classification and identification of possible catalytic residues of a number of hot dog fold-containing hypothetical proteins whose structures were determined in high throughput structural genomics projects.

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(R)-specific enoyl hydratases. a) prokaryotic (PDB code: 1IQ6) and b) eukaryotic (PDB code: 1PN2) origin. The structural motif of this subfamily – the overhanging segment is highlighted.
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Figure 6: (R)-specific enoyl hydratases. a) prokaryotic (PDB code: 1IQ6) and b) eukaryotic (PDB code: 1PN2) origin. The structural motif of this subfamily – the overhanging segment is highlighted.

Mentions: (R)-specific enoyl hydratase that catalyzes the hydration of trans-2-enoyl-CoA to (R)-3-hydroxyacyl-CoA is involved in supplying the (R)-3-hydroxyacyl-CoA from the fatty acid oxidation pathway to the polyhydroxy alkanoate (PHA) biosynthesis pathway [29]. The eukaryotic enzyme is found to be an integral part of a peroxisomal multifunctional protein (MFE-2 in fungi and MFE-1 in mammals) [4,30-32]. The crystal structures of a prokaryotic (R)-hydratase (PDB code: 1IQ6) from Aeromonas caviae, a eukaryotic hydratase 2 (PDB code: 1PN2) from Candida tropicalis and a human enzyme (PDB code: 1S9C) are available. In these structures, the loop corresponding to the one containing the catalytic histidine of the dehydratase FabA of E. coli, is longer by about 35 residues. This additional segment called the 'overhanging segment' contains both the catalytic residues Asp31 and His36 in 1IQ6. The prokaryotic enzyme forms a dimer of hot dogs with two such segments i.e., two catalytic sites, while the eukaryotic and human hydratases are dimers of double hot dogs, with each subunit having one catalytic site (Fig. 6). The double hot dog of eukaryotic and human hydratase 2, supposed to have arisen due to gene duplication, has structurally diverged during evolution to accommodate bulky fatty enoyl-CoAs at the cost of one catalytic site [3,33,34].


Analysis of proteins with the 'hot dog' fold: prediction of function and identification of catalytic residues of hypothetical proteins.

Pidugu LS, Maity K, Ramaswamy K, Surolia N, Suguna K - BMC Struct. Biol. (2009)

(R)-specific enoyl hydratases. a) prokaryotic (PDB code: 1IQ6) and b) eukaryotic (PDB code: 1PN2) origin. The structural motif of this subfamily – the overhanging segment is highlighted.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2698920&req=5

Figure 6: (R)-specific enoyl hydratases. a) prokaryotic (PDB code: 1IQ6) and b) eukaryotic (PDB code: 1PN2) origin. The structural motif of this subfamily – the overhanging segment is highlighted.
Mentions: (R)-specific enoyl hydratase that catalyzes the hydration of trans-2-enoyl-CoA to (R)-3-hydroxyacyl-CoA is involved in supplying the (R)-3-hydroxyacyl-CoA from the fatty acid oxidation pathway to the polyhydroxy alkanoate (PHA) biosynthesis pathway [29]. The eukaryotic enzyme is found to be an integral part of a peroxisomal multifunctional protein (MFE-2 in fungi and MFE-1 in mammals) [4,30-32]. The crystal structures of a prokaryotic (R)-hydratase (PDB code: 1IQ6) from Aeromonas caviae, a eukaryotic hydratase 2 (PDB code: 1PN2) from Candida tropicalis and a human enzyme (PDB code: 1S9C) are available. In these structures, the loop corresponding to the one containing the catalytic histidine of the dehydratase FabA of E. coli, is longer by about 35 residues. This additional segment called the 'overhanging segment' contains both the catalytic residues Asp31 and His36 in 1IQ6. The prokaryotic enzyme forms a dimer of hot dogs with two such segments i.e., two catalytic sites, while the eukaryotic and human hydratases are dimers of double hot dogs, with each subunit having one catalytic site (Fig. 6). The double hot dog of eukaryotic and human hydratase 2, supposed to have arisen due to gene duplication, has structurally diverged during evolution to accommodate bulky fatty enoyl-CoAs at the cost of one catalytic site [3,33,34].

Bottom Line: The hot dog fold has been found in more than sixty proteins since the first report of its existence about a decade ago.This study reveals that though the basic architecture of the fold is well conserved in these proteins, significant differences exist in their sequence, nature of substrate and oligomerization.The analysis led to predictions regarding the functional classification and identification of possible catalytic residues of a number of hot dog fold-containing hypothetical proteins whose structures were determined in high throughput structural genomics projects.

View Article: PubMed Central - HTML - PubMed

Affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India. plsmukhi@gmail.com

ABSTRACT

Background: The hot dog fold has been found in more than sixty proteins since the first report of its existence about a decade ago. The fold appears to have a strong association with fatty acid biosynthesis, its regulation and metabolism, as the proteins with this fold are predominantly coenzyme A-binding enzymes with a variety of substrates located at their active sites.

Results: We have analyzed the structural features and sequences of proteins having the hot dog fold. This study reveals that though the basic architecture of the fold is well conserved in these proteins, significant differences exist in their sequence, nature of substrate and oligomerization. Segments with certain conserved sequence motifs seem to play crucial structural and functional roles in various classes of these proteins.

Conclusion: The analysis led to predictions regarding the functional classification and identification of possible catalytic residues of a number of hot dog fold-containing hypothetical proteins whose structures were determined in high throughput structural genomics projects.

Show MeSH