1ppj: Difference between revisions

Revision as of 15:31, 21 February 2008

Bovine cytochrome bc1 complex with stigmatellin and antimycin

OverviewOverview

Antimycin A (antimycin), one of the first known and most potent inhibitors of the mitochondrial respiratory chain, binds to the quinone reduction site of the cytochrome bc1 complex. Structure-activity relationship studies have shown that the N-formylamino-salicyl-amide group is responsible for most of the binding specificity, and suggested that a low pKa for the phenolic OH group and an intramolecular H-bond between that OH and the carbonyl O of the salicylamide linkage are important. Two previous X-ray structures of antimycin bound to vertebrate bc1 complex gave conflicting results. A new structure reported here of the bovine mitochondrial bc1 complex at 2.28 A resolution with antimycin bound, allows us for the first time to reliably describe the binding of antimycin and shows that the intramolecular hydrogen bond described in solution and in the small-molecule structure is replaced by one involving the NH rather than carbonyl O of the amide linkage, with rotation of the amide group relative to the aromatic ring. The phenolic OH and formylamino N form H-bonds with conserved Asp228 of cytochrome b, and the formylamino O H-bonds via a water molecule to Lys227. A strong density, the right size and shape for a diatomic molecule is found between the other side of the dilactone ring and the alphaA helix.

About this StructureAbout this Structure

1PPJ 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

Binding of the respiratory chain inhibitor antimycin to the mitochondrial bc1 complex: a new crystal structure reveals an altered intramolecular hydrogen-bonding pattern., Huang LS, Cobessi D, Tung EY, Berry EA, J Mol Biol. 2005 Aug 19;351(3):573-97. PMID:16024040

Page seeded by OCA on Thu Feb 21 14:31:09 2008

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OCA

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-[[Image:1ppj.gif|left|200px]]<br /><applet load="1ppj" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1ppj.gif|left|200px]]<br /><applet load="1ppj" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1ppj, resolution 2.10&Aring;" />
 '''Bovine cytochrome bc1 complex with stigmatellin and antimycin'''<br />
 ==Overview==
-Antimycin A (antimycin), one of the first known and most potent inhibitors, of the mitochondrial respiratory chain, binds to the quinone reduction, site of the cytochrome bc1 complex. Structure-activity relationship, studies have shown that the N-formylamino-salicyl-amide group is, responsible for most of the binding specificity, and suggested that a low, pKa for the phenolic OH group and an intramolecular H-bond between that OH, and the carbonyl O of the salicylamide linkage are important. Two previous, X-ray structures of antimycin bound to vertebrate bc1 complex gave, conflicting results. A new structure reported here of the bovine, mitochondrial bc1 complex at 2.28 A resolution with antimycin bound, allows us for the first time to reliably describe the binding of antimycin, and shows that the intramolecular hydrogen bond described in solution and, in the small-molecule structure is replaced by one involving the NH rather, than carbonyl O of the amide linkage, with rotation of the amide group, relative to the aromatic ring. The phenolic OH and formylamino N form, H-bonds with conserved Asp228 of cytochrome b, and the formylamino O, H-bonds via a water molecule to Lys227. A strong density, the right size, and shape for a diatomic molecule is found between the other side of the, dilactone ring and the alphaA helix.
+Antimycin A (antimycin), one of the first known and most potent inhibitors of the mitochondrial respiratory chain, binds to the quinone reduction site of the cytochrome bc1 complex. Structure-activity relationship studies have shown that the N-formylamino-salicyl-amide group is responsible for most of the binding specificity, and suggested that a low pKa for the phenolic OH group and an intramolecular H-bond between that OH and the carbonyl O of the salicylamide linkage are important. Two previous X-ray structures of antimycin bound to vertebrate bc1 complex gave conflicting results. A new structure reported here of the bovine mitochondrial bc1 complex at 2.28 A resolution with antimycin bound, allows us for the first time to reliably describe the binding of antimycin and shows that the intramolecular hydrogen bond described in solution and in the small-molecule structure is replaced by one involving the NH rather than carbonyl O of the amide linkage, with rotation of the amide group relative to the aromatic ring. The phenolic OH and formylamino N form H-bonds with conserved Asp228 of cytochrome b, and the formylamino O H-bonds via a water molecule to Lys227. A strong density, the right size and shape for a diatomic molecule is found between the other side of the dilactone ring and the alphaA helix.
 ==About this Structure==
-PPJ 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 BHG, AZI, PO4, HEM, HEC, FES, SMA, CDL, PEE, ANY and GOL 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=1PPJ OCA].
+PPJ 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=BHG:'>BHG</scene>, <scene name='pdbligand=AZI:'>AZI</scene>, <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=HEM:'>HEM</scene>, <scene name='pdbligand=HEC:'>HEC</scene>, <scene name='pdbligand=FES:'>FES</scene>, <scene name='pdbligand=SMA:'>SMA</scene>, <scene name='pdbligand=CDL:'>CDL</scene>, <scene name='pdbligand=PEE:'>PEE</scene>, <scene name='pdbligand=ANY:'>ANY</scene> and <scene name='pdbligand=GOL:'>GOL</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=1PPJ OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Protein complex]]
 [[Category: Ubiquinol--cytochrome-c reductase]]
-[[Category: Berry, E.A.]]
+[[Category: Berry, E A.]]
 [[Category: Cobessi, D.]]
-[[Category: Huang, L.S.]]
+[[Category: Huang, L S.]]
-[[Category: Tung, E.Y.]]
+[[Category: Tung, E Y.]]
 [[Category: ANY]]
 [[Category: AZI]]
@@ Line 44: / Line 44: @@
 [[Category: stigmatellin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 23:59:57 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:31:09 2008''