1ylv: Difference between revisions
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[[Image:1ylv.jpg|left|200px]]<br /><applet load="1ylv" size=" | [[Image:1ylv.jpg|left|200px]]<br /><applet load="1ylv" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1ylv, resolution 2.15Å" /> | caption="1ylv, resolution 2.15Å" /> | ||
'''SCHIFF-BASE COMPLEX OF YEAST 5-AMINOLAEVULINIC ACID DEHYDRATASE WITH LAEVULINIC ACID'''<br /> | '''SCHIFF-BASE COMPLEX OF YEAST 5-AMINOLAEVULINIC ACID DEHYDRATASE WITH LAEVULINIC ACID'''<br /> | ||
==Overview== | ==Overview== | ||
The X-ray structure of the complex formed between yeast 5-aminolaevulinic | The X-ray structure of the complex formed between yeast 5-aminolaevulinic acid dehydratase (ALAD) and the inhibitor laevulinic acid has been determined at 2.15 A resolution. The inhibitor binds by forming a Schiff base link with one of the two invariant lysines at the catalytic center: Lys263. It is known that this lysine forms a Schiff base link with substrate bound at the enzyme's so-called P-site. The carboxyl group of laevulinic acid makes hydrogen bonds with the side-chain-OH groups of Tyr329 and Ser290, as well as with the main-chain >NH group of Ser290. The aliphatic moiety of the inhibitor makes hydrophobic interactions with surrounding aromatic residues in the protein including Phe219, which resides in the flap covering the active site. Our analysis strongly suggests that the same interactions will be made by P-side substrate and also indicates that the substrate that binds at the enzyme's A-site will interact with the enzyme's zinc ion bound by three cysteines (133, 135, and 143). Inhibitor binding caused a substantial ordering of the active site flap (residues 217-235), which was largely invisible in the native electron density map and indicates that this highly conserved yet flexible region has a specific role in substrate binding during catalysis. | ||
==About this Structure== | ==About this Structure== | ||
1YLV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with ZN and SHF as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Porphobilinogen_synthase Porphobilinogen synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.24 4.2.1.24] Full crystallographic information is available from [http:// | 1YLV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=SHF:'>SHF</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Porphobilinogen_synthase Porphobilinogen synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.24 4.2.1.24] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YLV OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Coker, A.]] | [[Category: Coker, A.]] | ||
[[Category: Cooper, J | [[Category: Cooper, J B.]] | ||
[[Category: Erskine, P | [[Category: Erskine, P T.]] | ||
[[Category: Newbold, R.]] | [[Category: Newbold, R.]] | ||
[[Category: Roper, J.]] | [[Category: Roper, J.]] | ||
[[Category: Shoolingin-Jordan, P | [[Category: Shoolingin-Jordan, P M.]] | ||
[[Category: Warren, M | [[Category: Warren, M J.]] | ||
[[Category: Wood, S | [[Category: Wood, S P.]] | ||
[[Category: SHF]] | [[Category: SHF]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
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[[Category: tim barrel]] | [[Category: tim barrel]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:06:46 2008'' | ||
Revision as of 17:06, 21 February 2008
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SCHIFF-BASE COMPLEX OF YEAST 5-AMINOLAEVULINIC ACID DEHYDRATASE WITH LAEVULINIC ACID
OverviewOverview
The X-ray structure of the complex formed between yeast 5-aminolaevulinic acid dehydratase (ALAD) and the inhibitor laevulinic acid has been determined at 2.15 A resolution. The inhibitor binds by forming a Schiff base link with one of the two invariant lysines at the catalytic center: Lys263. It is known that this lysine forms a Schiff base link with substrate bound at the enzyme's so-called P-site. The carboxyl group of laevulinic acid makes hydrogen bonds with the side-chain-OH groups of Tyr329 and Ser290, as well as with the main-chain >NH group of Ser290. The aliphatic moiety of the inhibitor makes hydrophobic interactions with surrounding aromatic residues in the protein including Phe219, which resides in the flap covering the active site. Our analysis strongly suggests that the same interactions will be made by P-side substrate and also indicates that the substrate that binds at the enzyme's A-site will interact with the enzyme's zinc ion bound by three cysteines (133, 135, and 143). Inhibitor binding caused a substantial ordering of the active site flap (residues 217-235), which was largely invisible in the native electron density map and indicates that this highly conserved yet flexible region has a specific role in substrate binding during catalysis.
About this StructureAbout this Structure
1YLV is a Single protein structure of sequence from Saccharomyces cerevisiae with and as ligands. Active as Porphobilinogen synthase, with EC number 4.2.1.24 Full crystallographic information is available from OCA.
ReferenceReference
The Schiff base complex of yeast 5-aminolaevulinic acid dehydratase with laevulinic acid., Erskine PT, Newbold R, Roper J, Coker A, Warren MJ, Shoolingin-Jordan PM, Wood SP, Cooper JB, Protein Sci. 1999 Jun;8(6):1250-6. PMID:10386874
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