2dkc
From Proteopedia
(New page: 200px<br /><applet load="2dkc" size="450" color="white" frame="true" align="right" spinBox="true" caption="2dkc, resolution 2.20Å" /> '''Crystal structure of...) |
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| - | [[Image:2dkc.gif|left|200px]]<br /><applet load="2dkc" size=" | + | [[Image:2dkc.gif|left|200px]]<br /><applet load="2dkc" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2dkc, resolution 2.20Å" /> | caption="2dkc, resolution 2.20Å" /> | ||
'''Crystal structure of N-acetylglucosamine-phosphate mutase, a member of the alpha-D-phosphohexomutase superfamily, in the substrate complex'''<br /> | '''Crystal structure of N-acetylglucosamine-phosphate mutase, a member of the alpha-D-phosphohexomutase superfamily, in the substrate complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | N-acetylglucosamine-phosphate mutase (AGM1) is an essential enzyme in the | + | N-acetylglucosamine-phosphate mutase (AGM1) is an essential enzyme in the synthetic process of UDP-N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is a UDP sugar that serves as a biosynthetic precursor of glycoproteins, mucopolysaccharides, and the cell wall of bacteria. Thus, a specific inhibitor of AGM1 from pathogenetic fungi could be a new candidate for an antifungal reagent that inhibits cell wall synthesis. AGM1 catalyzes the conversion of N-acetylglucosamine 6-phosphate (GlcNAc-6-P) into N-acetylglucosamine 1-phosphate (GlcNAc-1-P). This enzyme is a member of the alpha-D-phosphohexomutase superfamily, which catalyzes the intramolecular phosphoryl transfer of sugar substrates. Here we report the crystal structures of AGM1 from Candida albicans for the first time, both in the apoform and in the complex forms with the substrate and the product, and discuss its catalytic mechanism. The structure of AGM1 consists of four domains, of which three domains have essentially the same fold. The overall structure is similar to those of phosphohexomutases; however, there are two additional beta-strands in domain 4, and a circular permutation occurs in domain 1. The catalytic cleft is formed by four loops from each domain. The N-acetyl group of the substrate is recognized by Val-370 and Asn-389 in domain 3, from which the substrate specificity arises. By comparing the substrate and product complexes, it is suggested that the substrate rotates about 180 degrees on the axis linking C-4 and the midpoint of the C-5-O-5 bond in the reaction. |
==About this Structure== | ==About this Structure== | ||
| - | 2DKC 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 16G, PO4 and ZN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoacetylglucosamine_mutase Phosphoacetylglucosamine mutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.2.3 5.4.2.3] Full crystallographic information is available from [http:// | + | 2DKC 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=16G:'>16G</scene>, <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoacetylglucosamine_mutase Phosphoacetylglucosamine mutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.2.3 5.4.2.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DKC OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Phosphoacetylglucosamine mutase]] | [[Category: Phosphoacetylglucosamine mutase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Fukami, T | + | [[Category: Fukami, T A.]] |
[[Category: Kita, A.]] | [[Category: Kita, A.]] | ||
[[Category: Maruyama, D.]] | [[Category: Maruyama, D.]] | ||
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[[Category: mutase]] | [[Category: mutase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:59:39 2008'' |
Revision as of 14:59, 21 February 2008
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Crystal structure of N-acetylglucosamine-phosphate mutase, a member of the alpha-D-phosphohexomutase superfamily, in the substrate complex
Overview
N-acetylglucosamine-phosphate mutase (AGM1) is an essential enzyme in the synthetic process of UDP-N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is a UDP sugar that serves as a biosynthetic precursor of glycoproteins, mucopolysaccharides, and the cell wall of bacteria. Thus, a specific inhibitor of AGM1 from pathogenetic fungi could be a new candidate for an antifungal reagent that inhibits cell wall synthesis. AGM1 catalyzes the conversion of N-acetylglucosamine 6-phosphate (GlcNAc-6-P) into N-acetylglucosamine 1-phosphate (GlcNAc-1-P). This enzyme is a member of the alpha-D-phosphohexomutase superfamily, which catalyzes the intramolecular phosphoryl transfer of sugar substrates. Here we report the crystal structures of AGM1 from Candida albicans for the first time, both in the apoform and in the complex forms with the substrate and the product, and discuss its catalytic mechanism. The structure of AGM1 consists of four domains, of which three domains have essentially the same fold. The overall structure is similar to those of phosphohexomutases; however, there are two additional beta-strands in domain 4, and a circular permutation occurs in domain 1. The catalytic cleft is formed by four loops from each domain. The N-acetyl group of the substrate is recognized by Val-370 and Asn-389 in domain 3, from which the substrate specificity arises. By comparing the substrate and product complexes, it is suggested that the substrate rotates about 180 degrees on the axis linking C-4 and the midpoint of the C-5-O-5 bond in the reaction.
About this Structure
2DKC is a Single protein structure of sequence from Candida albicans with , and as ligands. Active as Phosphoacetylglucosamine mutase, with EC number 5.4.2.3 Full crystallographic information is available from OCA.
Reference
Crystal structures of N-acetylglucosamine-phosphate mutase, a member of the alpha-D-phosphohexomutase superfamily, and its substrate and product complexes., Nishitani Y, Maruyama D, Nonaka T, Kita A, Fukami TA, Mio T, Yamada-Okabe H, Yamada-Okabe T, Miki K, J Biol Chem. 2006 Jul 14;281(28):19740-7. Epub 2006 May 1. PMID:16651269
Page seeded by OCA on Thu Feb 21 16:59:39 2008
Categories: Candida albicans | Phosphoacetylglucosamine mutase | Single protein | Fukami, T A. | Kita, A. | Maruyama, D. | Miki, K. | Mio, T. | Nishitani, Y. | Nonaka, T. | Yamada-Okabe, H. | Yamada-Okabe, T. | 16G | PO4 | ZN | Mutase
