1iyk
From Proteopedia
(New page: 200px<br /><applet load="1iyk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1iyk, resolution 2.3Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1iyk.jpg|left|200px]]<br /><applet load="1iyk" size=" | + | [[Image:1iyk.jpg|left|200px]]<br /><applet load="1iyk" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1iyk, resolution 2.3Å" /> | caption="1iyk, resolution 2.3Å" /> | ||
'''CRYSTAL STRUCTURE OF CANDIDA ALBICANS N-MYRISTOYLTRANSFERASE WITH MYRISTOYL-COA AND PEPTIDIC INHIBITOR'''<br /> | '''CRYSTAL STRUCTURE OF CANDIDA ALBICANS N-MYRISTOYLTRANSFERASE WITH MYRISTOYL-COA AND PEPTIDIC INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Myristoyl-CoA:protein N-myristoyltransferase (Nmt) is a monomeric enzyme | + | Myristoyl-CoA:protein N-myristoyltransferase (Nmt) is a monomeric enzyme that catalyzes the transfer of the fatty acid myristate from myristoyl-CoA to the N-terminal glycine residue of a variety of eukaryotic and viral proteins. Genetic and biochemical studies have established that Nmt is an attractive target for antifungal drugs. We present here crystal structures of C. albicans Nmt complexed with two classes of inhibitor competitive for peptide substrates. One is a peptidic inhibitor designed from the peptide substrate; the other is a nonpeptidic inhibitor having a benzofuran core. Both inhibitors are bound into the same binding groove, generated by some structural rearrangements of the enzyme, with the peptidic inhibitor showing a substrate-like binding mode and the nonpeptidic inhibitor binding differently. Further, site-directed mutagenesis for C. albicans Nmt has been utilized in order to define explicitly which amino acids are critical for inhibitor binding. The results suggest that the enzyme has some degree of flexibility for substrate binding and provide valuable information for inhibitor design. |
==About this Structure== | ==About this Structure== | ||
| - | 1IYK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Candida_albicans Candida albicans] with MYA and MIM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glycylpeptide_N-tetradecanoyltransferase Glycylpeptide N-tetradecanoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.97 2.3.1.97] Full crystallographic information is available from [http:// | + | 1IYK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Candida_albicans Candida albicans] with <scene name='pdbligand=MYA:'>MYA</scene> and <scene name='pdbligand=MIM:'>MIM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glycylpeptide_N-tetradecanoyltransferase Glycylpeptide N-tetradecanoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.97 2.3.1.97] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IYK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Aoki, Y.]] | [[Category: Aoki, Y.]] | ||
| - | [[Category: Arcy, A | + | [[Category: Arcy, A D.]] |
| - | [[Category: Banner, D | + | [[Category: Banner, D W.]] |
| - | [[Category: Fukami, T | + | [[Category: Fukami, T A.]] |
[[Category: Morikami, K.]] | [[Category: Morikami, K.]] | ||
[[Category: Ohtsuka, T.]] | [[Category: Ohtsuka, T.]] | ||
[[Category: Shiratori, Y.]] | [[Category: Shiratori, Y.]] | ||
[[Category: Sogabe, S.]] | [[Category: Sogabe, S.]] | ||
| - | [[Category: Winkler, F | + | [[Category: Winkler, F K.]] |
[[Category: MIM]] | [[Category: MIM]] | ||
[[Category: MYA]] | [[Category: MYA]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:17:02 2008'' |
Revision as of 11:17, 21 February 2008
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CRYSTAL STRUCTURE OF CANDIDA ALBICANS N-MYRISTOYLTRANSFERASE WITH MYRISTOYL-COA AND PEPTIDIC INHIBITOR
Overview
Myristoyl-CoA:protein N-myristoyltransferase (Nmt) is a monomeric enzyme that catalyzes the transfer of the fatty acid myristate from myristoyl-CoA to the N-terminal glycine residue of a variety of eukaryotic and viral proteins. Genetic and biochemical studies have established that Nmt is an attractive target for antifungal drugs. We present here crystal structures of C. albicans Nmt complexed with two classes of inhibitor competitive for peptide substrates. One is a peptidic inhibitor designed from the peptide substrate; the other is a nonpeptidic inhibitor having a benzofuran core. Both inhibitors are bound into the same binding groove, generated by some structural rearrangements of the enzyme, with the peptidic inhibitor showing a substrate-like binding mode and the nonpeptidic inhibitor binding differently. Further, site-directed mutagenesis for C. albicans Nmt has been utilized in order to define explicitly which amino acids are critical for inhibitor binding. The results suggest that the enzyme has some degree of flexibility for substrate binding and provide valuable information for inhibitor design.
About this Structure
1IYK is a Single protein structure of sequence from Candida albicans with and as ligands. Active as Glycylpeptide N-tetradecanoyltransferase, with EC number 2.3.1.97 Full crystallographic information is available from OCA.
Reference
Crystal structures of Candida albicans N-myristoyltransferase with two distinct inhibitors., Sogabe S, Masubuchi M, Sakata K, Fukami TA, Morikami K, Shiratori Y, Ebiike H, Kawasaki K, Aoki Y, Shimma N, D'Arcy A, Winkler FK, Banner DW, Ohtsuka T, Chem Biol. 2002 Oct;9(10):1119-28. PMID:12401496
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