Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.3.14 (
ATP synthase
)
7,042
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mitochondrial ATP synthases, the major producers of ATP in higher eukaryotic cells, are known to be regulated by a peptide designated IF(1). In contrast, in yeast three such peptides have been identified, IF(1) and
STF
(1), which inhibit the reverse ATPase reaction, and
STF
(2), a modulator of the action of these inhibitors. Despite significant homology to IF(1),
STF
(1) exhibits less than half ( approximately 40%) its inhibitory potency. The two-fold purpose of this bioinformatic study was to gain structural insight into the different inhibitory potencies of IF(1) and
STF
(1) and to determine to what extent yeast are unique in employing multiple peptides to regulate the
ATP synthase
. Sequence and secondary structural analyses and comparison with the known structure of bovine IF(1) predicted a dimeric structure for yeast
STF
(1) in which the C-terminal regions form a coiled-coil. Moreover, sequence comparisons showed that within this C-terminal region a conserved acidic residue (Asp 59) in yeast IF(1) is replaced by Asn in
STF
(1). In the known structure of bovine IF(1), predicted to be very similar to that of yeast IF(1), the residue Glu 68 corresponding to Asp 59 participates in the formation of a four-residue conserved acidic cluster in the middle of the coiled-coil in the C-terminal region. It is deduced here that this acidic cluster is likely to be important in the regulation of IF(1)'s inhibitory capacity and that replacement of conserved Asp 59 by Asn in
STF
(1) may reduce its potency. Although other homologs to the inhibitors IF(1) and
STF
(1) were not found in searches of available eukaryotic genomes, including human, a new homolog, named
STF
(3), with 65% identity to the modulator
STF
(2), was discovered within the yeast genome and identified to be expressed by searching the yeast EST database. Thus, yeast appears unique in regulating the
ATP synthase
by involving multiple peptides (IF(1),
STF
(1),
STF
(2), and perhaps
STF
(3)).
...
PMID:ATP synthase of yeast: structural insight into the different inhibitory potencies of two regulatory peptides and identification of a new potential regulator. 1217 55
In Saccharomyces cerevisiae, at least three proteins (IF(1),
STF
(1), and
STF
(2)) appear to be involved in the regulation of
ATP synthase
. Both IF(1) and
STF
(1) inhibit F(1), whereas the proposed function for
STF
(2) is to facilitate the binding of IF(1) and
STF
(1) to F(1). The oligomerization properties of yeast IF(1) and
STF
(1) have been investigated by sedimentation equilibrium analytical ultracentrifugation and by covalent cross-linking. Both techniques confirm that IF(1) and
STF
(1) oligomerize in opposite directions in relation to pH, suggesting that both proteins might regulate yeast F(1)F(0)-ATPase under different conditions. Their effects on bovine F-ATPases are also described. Whereas bovine IF(1) inhibits yeast F(1)-ATPase even better than yeast IF(1) or
STF
(1), the capability of yeast IF(1) to inhibit the bovine enzyme is very low and decreases with time. Such an effect is also observed in the study of the homologous inhibition of yeast F(1)-ATPase. Yeast inhibitors are not as effective as their bovine counterpart, and the complex seems to dissociate gradually.
...
PMID:Homologous and heterologous inhibitory effects of ATPase inhibitor proteins on F-ATPases. 1218 78
