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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.

Show MeSH
The active site tunnel in different forms of P. falciparum FabZ. a) active hexameric (PDB code: 1Z6B) and b) inactive dimeric form of FabZ from P. falciparum (PDB code:1ZHG). The inhibitor 3-decenoyl-NAC has been manually docked into the active sites and shown in mesh representation for highlighting the tunnels.
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Figure 11: The active site tunnel in different forms of P. falciparum FabZ. a) active hexameric (PDB code: 1Z6B) and b) inactive dimeric form of FabZ from P. falciparum (PDB code:1ZHG). The inhibitor 3-decenoyl-NAC has been manually docked into the active sites and shown in mesh representation for highlighting the tunnels.

Mentions: The third enzyme in which structural changes have been observed is FabZ of P. falciparum (PDB codes: 1Z6B &1ZHG). As reported earlier [6], the two cis peptide bonds in the active site loops of the active hexameric FabZ molecule flip to trans peptide bonds, leading to large conformational changes in the active site loops, by which the architecture of the catalytic site drastically changes making it incapable of binding to the substrate (Fig. 11). In addition, the hexamer dissociates into inactive dimers as the changes affect the loops at the hexamer interfaces. Extensive Dynamic Light Scattering and gel filtration studies showed that these transitions are triggered by pH changes.


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)

The active site tunnel in different forms of P. falciparum FabZ. a) active hexameric (PDB code: 1Z6B) and b) inactive dimeric form of FabZ from P. falciparum (PDB code:1ZHG). The inhibitor 3-decenoyl-NAC has been manually docked into the active sites and shown in mesh representation for highlighting the tunnels.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 11: The active site tunnel in different forms of P. falciparum FabZ. a) active hexameric (PDB code: 1Z6B) and b) inactive dimeric form of FabZ from P. falciparum (PDB code:1ZHG). The inhibitor 3-decenoyl-NAC has been manually docked into the active sites and shown in mesh representation for highlighting the tunnels.
Mentions: The third enzyme in which structural changes have been observed is FabZ of P. falciparum (PDB codes: 1Z6B &1ZHG). As reported earlier [6], the two cis peptide bonds in the active site loops of the active hexameric FabZ molecule flip to trans peptide bonds, leading to large conformational changes in the active site loops, by which the architecture of the catalytic site drastically changes making it incapable of binding to the substrate (Fig. 11). In addition, the hexamer dissociates into inactive dimers as the changes affect the loops at the hexamer interfaces. Extensive Dynamic Light Scattering and gel filtration studies showed that these transitions are triggered by pH changes.

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