2pb1
From Proteopedia
(New page: 200px<br /><applet load="2pb1" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pb1, resolution 1.900Å" /> '''Exo-B-(1,3)-Glucana...) |
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| - | [[Image:2pb1.gif|left|200px]]<br /><applet load="2pb1" size=" | + | [[Image:2pb1.gif|left|200px]]<br /><applet load="2pb1" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2pb1, resolution 1.900Å" /> | caption="2pb1, resolution 1.900Å" /> | ||
'''Exo-B-(1,3)-Glucanase from Candida Albicans in complex with unhydrolysed and covalently linked 2,4-dinitrophenyl-2-deoxy-2-fluoro-B-D-glucopyranoside at 1.9 A'''<br /> | '''Exo-B-(1,3)-Glucanase from Candida Albicans in complex with unhydrolysed and covalently linked 2,4-dinitrophenyl-2-deoxy-2-fluoro-B-D-glucopyranoside at 1.9 A'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A group of fungal exo-beta-(1,3)-glucanases, including that from the human | + | A group of fungal exo-beta-(1,3)-glucanases, including that from the human pathogen Candida albicans (Exg), belong to glycosyl hydrolase family 5 that also includes many bacterial cellulases (endo-beta-1, 4-glucanases). Family members, despite wide sequence variations, share a common mechanism and are characterised by possessing eight invariant residues making up the active site. These include two glutamate residues acting as nucleophile and acid/base, respectively. Exg is an abundant secreted enzyme possessing both hydrolase and transferase activity consistent with a role in cell wall glucan metabolism and possibly morphogenesis. The structures of Exg in both free and inhibited forms have been determined to 1.9 A resolution. A distorted (beta/alpha)8 barrel structure accommodates an active site which is located within a deep pocket, formed when extended loop regions close off a cellulase-like groove. Structural analysis of a covalently bound mechanism-based inhibitor (2-fluoroglucosylpyranoside) and of a transition-state analogue (castanospermine) has identified the binding interactions at the -1 glucose binding site. In particular the carboxylate of Glu27 serves a dominant hydrogen-bonding role. Access by a 1,3-glucan chain to the pocket in Exg can be understood in terms of a change in conformation of the terminal glucose residue from chair to twisted boat. The geometry of the pocket is not, however, well suited for cleavage of 1,4-glycosidic linkages. A second glucose site was identified at the entrance to the pocket, sandwiched between two antiparallel phenylalanine side-chains. This aromatic entrance-way must not only direct substrate into the pocket but also may act as a clamp for an acceptor molecule participating in the transfer reaction. |
==About this Structure== | ==About this Structure== | ||
| - | 2PB1 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 G2F and NFG as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glucan_1,3-beta-glucosidase Glucan 1,3-beta-glucosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.58 3.2.1.58] Full crystallographic information is available from [http:// | + | 2PB1 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=G2F:'>G2F</scene> and <scene name='pdbligand=NFG:'>NFG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glucan_1,3-beta-glucosidase Glucan 1,3-beta-glucosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.58 3.2.1.58] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PB1 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Glucan 1,3-beta-glucosidase]] | [[Category: Glucan 1,3-beta-glucosidase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cutfield, J | + | [[Category: Cutfield, J F.]] |
| - | [[Category: Cutfield, S | + | [[Category: Cutfield, S M.]] |
| - | [[Category: Davies, G | + | [[Category: Davies, G J.]] |
| - | [[Category: Sullivan, P | + | [[Category: Sullivan, P A.]] |
[[Category: G2F]] | [[Category: G2F]] | ||
[[Category: NFG]] | [[Category: NFG]] | ||
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[[Category: mechanism-based inhibitor]] | [[Category: mechanism-based inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:27:48 2008'' |
Revision as of 16:27, 21 February 2008
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Exo-B-(1,3)-Glucanase from Candida Albicans in complex with unhydrolysed and covalently linked 2,4-dinitrophenyl-2-deoxy-2-fluoro-B-D-glucopyranoside at 1.9 A
Overview
A group of fungal exo-beta-(1,3)-glucanases, including that from the human pathogen Candida albicans (Exg), belong to glycosyl hydrolase family 5 that also includes many bacterial cellulases (endo-beta-1, 4-glucanases). Family members, despite wide sequence variations, share a common mechanism and are characterised by possessing eight invariant residues making up the active site. These include two glutamate residues acting as nucleophile and acid/base, respectively. Exg is an abundant secreted enzyme possessing both hydrolase and transferase activity consistent with a role in cell wall glucan metabolism and possibly morphogenesis. The structures of Exg in both free and inhibited forms have been determined to 1.9 A resolution. A distorted (beta/alpha)8 barrel structure accommodates an active site which is located within a deep pocket, formed when extended loop regions close off a cellulase-like groove. Structural analysis of a covalently bound mechanism-based inhibitor (2-fluoroglucosylpyranoside) and of a transition-state analogue (castanospermine) has identified the binding interactions at the -1 glucose binding site. In particular the carboxylate of Glu27 serves a dominant hydrogen-bonding role. Access by a 1,3-glucan chain to the pocket in Exg can be understood in terms of a change in conformation of the terminal glucose residue from chair to twisted boat. The geometry of the pocket is not, however, well suited for cleavage of 1,4-glycosidic linkages. A second glucose site was identified at the entrance to the pocket, sandwiched between two antiparallel phenylalanine side-chains. This aromatic entrance-way must not only direct substrate into the pocket but also may act as a clamp for an acceptor molecule participating in the transfer reaction.
About this Structure
2PB1 is a Single protein structure of sequence from Candida albicans with and as ligands. Active as Glucan 1,3-beta-glucosidase, with EC number 3.2.1.58 Full crystallographic information is available from OCA.
Reference
The structure of the exo-beta-(1,3)-glucanase from Candida albicans in native and bound forms: relationship between a pocket and groove in family 5 glycosyl hydrolases., Cutfield SM, Davies GJ, Murshudov G, Anderson BF, Moody PC, Sullivan PA, Cutfield JF, J Mol Biol. 1999 Dec 3;294(3):771-83. PMID:10610795
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