1sqx: Difference between revisions

Revision as of 16:04, 21 February 2008

Crystal Structure Analysis of Bovine Bc1 with Stigmatellin A

OverviewOverview

Cytochrome bc(1) is an integral membrane protein complex essential for cellular respiration and photosynthesis; it couples electron transfer from quinol to cytochrome c to proton translocation across the membrane. Specific bc(1) inhibitors have not only played crucial roles in elucidating the mechanism of bc(1) function but have also provided leads for the development of novel antibiotics. Crystal structures of bovine bc(1) in complex with the specific Q(o) site inhibitors azoxystrobin, MOAS, myxothiazol, stigmatellin and 5-undecyl-6-hydroxy-4,7-dioxobenzothiazole were determined. Interactions, conformational changes and possible mechanisms of resistance, specific to each inhibitor, were defined. Residues and secondary structure elements that are capable of discriminating different classes of Q(o) site inhibitors were identified for the cytochrome b subunit. Directions in the displacement of the cd1 helix of cytochrome b subunit in response to various Q(o) site inhibitors were correlated to the binary conformational switch of the extrinsic domain of the iron-sulfur protein subunit. The new structural information, together with structures previously determined, provide a basis that, combined with biophysical and mutational data, suggest a modification to the existing classification of bc(1) inhibitors. bc(1) inhibitors are grouped into three classes: class P inhibitors bind to the Q(o) site, class N inhibitors bind to the Q(i) site and the class PN inhibitors target both sites. Class P contains two subgroups, Pm and Pf, that are distinct by their ability to induce mobile or fixed conformation of iron-sulfur protein.

About this StructureAbout this Structure

1SQX is a Protein complex structure of sequences from Bos taurus with , , and as ligands. Active as Ubiquinol--cytochrome-c reductase, with EC number 1.10.2.2 Full crystallographic information is available from OCA.

ReferenceReference

Crystallographic studies of quinol oxidation site inhibitors: a modified classification of inhibitors for the cytochrome bc(1) complex., Esser L, Quinn B, Li YF, Zhang M, Elberry M, Yu L, Yu CA, Xia D, J Mol Biol. 2004 Jul 30;341(1):281-302. PMID:15312779

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-[[Image:1sqx.gif|left|200px]]<br /><applet load="1sqx" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1sqx.gif|left|200px]]<br /><applet load="1sqx" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1sqx, resolution 2.60&Aring;" />
 '''Crystal Structure Analysis of Bovine Bc1 with Stigmatellin A'''<br />
 ==Overview==
-Cytochrome bc(1) is an integral membrane protein complex essential for, cellular respiration and photosynthesis; it couples electron transfer from, quinol to cytochrome c to proton translocation across the membrane., Specific bc(1) inhibitors have not only played crucial roles in, elucidating the mechanism of bc(1) function but have also provided leads, for the development of novel antibiotics. Crystal structures of bovine, bc(1) in complex with the specific Q(o) site inhibitors azoxystrobin, MOAS, myxothiazol, stigmatellin and, 5-undecyl-6-hydroxy-4,7-dioxobenzothiazole were determined. Interactions, conformational changes and possible mechanisms of resistance, specific to, each inhibitor, were defined. Residues and secondary structure elements, that are capable of discriminating different classes of Q(o) site, inhibitors were identified for the cytochrome b subunit. Directions in the, displacement of the cd1 helix of cytochrome b subunit in response to, various Q(o) site inhibitors were correlated to the binary conformational, switch of the extrinsic domain of the iron-sulfur protein subunit. The new, structural information, together with structures previously determined, provide a basis that, combined with biophysical and mutational data, suggest a modification to the existing classification of bc(1) inhibitors., bc(1) inhibitors are grouped into three classes: class P inhibitors bind, to the Q(o) site, class N inhibitors bind to the Q(i) site and the class, PN inhibitors target both sites. Class P contains two subgroups, Pm and, Pf, that are distinct by their ability to induce mobile or fixed, conformation of iron-sulfur protein.
+Cytochrome bc(1) is an integral membrane protein complex essential for cellular respiration and photosynthesis; it couples electron transfer from quinol to cytochrome c to proton translocation across the membrane. Specific bc(1) inhibitors have not only played crucial roles in elucidating the mechanism of bc(1) function but have also provided leads for the development of novel antibiotics. Crystal structures of bovine bc(1) in complex with the specific Q(o) site inhibitors azoxystrobin, MOAS, myxothiazol, stigmatellin and 5-undecyl-6-hydroxy-4,7-dioxobenzothiazole were determined. Interactions, conformational changes and possible mechanisms of resistance, specific to each inhibitor, were defined. Residues and secondary structure elements that are capable of discriminating different classes of Q(o) site inhibitors were identified for the cytochrome b subunit. Directions in the displacement of the cd1 helix of cytochrome b subunit in response to various Q(o) site inhibitors were correlated to the binary conformational switch of the extrinsic domain of the iron-sulfur protein subunit. The new structural information, together with structures previously determined, provide a basis that, combined with biophysical and mutational data, suggest a modification to the existing classification of bc(1) inhibitors. bc(1) inhibitors are grouped into three classes: class P inhibitors bind to the Q(o) site, class N inhibitors bind to the Q(i) site and the class PN inhibitors target both sites. Class P contains two subgroups, Pm and Pf, that are distinct by their ability to induce mobile or fixed conformation of iron-sulfur protein.
 ==About this Structure==
-SQX is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with FES, UQ2, HEM and SMA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Ubiquinol--cytochrome-c_reductase Ubiquinol--cytochrome-c reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.10.2.2 1.10.2.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1SQX OCA].
+SQX is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=FES:'>FES</scene>, <scene name='pdbligand=UQ2:'>UQ2</scene>, <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=SMA:'>SMA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Ubiquinol--cytochrome-c_reductase Ubiquinol--cytochrome-c reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.10.2.2 1.10.2.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SQX OCA].
 ==Reference==
@@ Line 16: / Line 16: @@
 [[Category: Elberry, M.]]
 [[Category: Esser, L.]]
-[[Category: Li, Y.F.]]
+[[Category: Li, Y F.]]
 [[Category: Quinn, B.]]
 [[Category: Xia, D.]]
-[[Category: Yu, C.A.]]
+[[Category: Yu, C A.]]
 [[Category: Yu, L.]]
 [[Category: Zhang, M.]]
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 [[Category: qo inhibitor]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 02:35:03 2007''
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