1hi4
From Proteopedia
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==Overview== | ==Overview== | ||
Eosinophil-derived neurotoxin (EDN), a basic ribonuclease found in the, large specific granules of eosinophils, belongs to the pancreatic RNase A, family. Although its physiological function is still unclear, it has been, shown that EDN is a neurotoxin capable of inducing the Gordon phenomenon, in rabbits. EDN is also a potent helminthotoxin and can mediate antiviral, activity of eosinophils against isolated virions of the respiratory, syncytial virus. EDN is a catalytically efficient RNase sharing similar, substrate specificity with pancreatic RNase A with its ribonucleolytic, activity being absolutely essential for its neurotoxic, helminthotoxic, and antiviral activities. The crystal structure of recombinant human EDN, in the unliganded form has been determined previously (Mosimann, S. C., Newton, D. L., Youle, R. J., and James, M. N. G. (1996) J. Mol. Biol. 260, 540-552). We have now determined high resolution (1.8 A) crystal, structures for EDN in complex with adenosine-3',5'-diphosphate, (3',5'-ADP), adenosine-2',5'-di-phosphate (2',5'-ADP), adenosine-5'-diphosphate (5'-ADP) as well as for a native structure in the, presence of sulfate refined at 1.6 A. The inhibition constant of these, mononucleotides for EDN has been determined. The structures present the, first detailed picture of differences between EDN and RNase A in substrate, recognition at the ribonucleolytic active site. They also provide a, starting point for the design of tight-binding inhibitors, which may be, used to restrain the RNase activity of EDN. | Eosinophil-derived neurotoxin (EDN), a basic ribonuclease found in the, large specific granules of eosinophils, belongs to the pancreatic RNase A, family. Although its physiological function is still unclear, it has been, shown that EDN is a neurotoxin capable of inducing the Gordon phenomenon, in rabbits. EDN is also a potent helminthotoxin and can mediate antiviral, activity of eosinophils against isolated virions of the respiratory, syncytial virus. EDN is a catalytically efficient RNase sharing similar, substrate specificity with pancreatic RNase A with its ribonucleolytic, activity being absolutely essential for its neurotoxic, helminthotoxic, and antiviral activities. The crystal structure of recombinant human EDN, in the unliganded form has been determined previously (Mosimann, S. C., Newton, D. L., Youle, R. J., and James, M. N. G. (1996) J. Mol. Biol. 260, 540-552). We have now determined high resolution (1.8 A) crystal, structures for EDN in complex with adenosine-3',5'-diphosphate, (3',5'-ADP), adenosine-2',5'-di-phosphate (2',5'-ADP), adenosine-5'-diphosphate (5'-ADP) as well as for a native structure in the, presence of sulfate refined at 1.6 A. The inhibition constant of these, mononucleotides for EDN has been determined. The structures present the, first detailed picture of differences between EDN and RNase A in substrate, recognition at the ribonucleolytic active site. They also provide a, starting point for the design of tight-binding inhibitors, which may be, used to restrain the RNase activity of EDN. | ||
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Central hypoventilation syndrome, congenital OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131242 131242]], Hirschsprung disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131242 131242]], Shah-Waardenburg syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131242 131242]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: rnase-2]] | [[Category: rnase-2]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:18:18 2007'' |
Revision as of 15:11, 12 November 2007
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EOSINOPHIL-DERIVED NEUROTOXIN (EDN)-ADENOSINE-3'-5'-DIPHOSPHATE COMPLEX
Contents |
Overview
Eosinophil-derived neurotoxin (EDN), a basic ribonuclease found in the, large specific granules of eosinophils, belongs to the pancreatic RNase A, family. Although its physiological function is still unclear, it has been, shown that EDN is a neurotoxin capable of inducing the Gordon phenomenon, in rabbits. EDN is also a potent helminthotoxin and can mediate antiviral, activity of eosinophils against isolated virions of the respiratory, syncytial virus. EDN is a catalytically efficient RNase sharing similar, substrate specificity with pancreatic RNase A with its ribonucleolytic, activity being absolutely essential for its neurotoxic, helminthotoxic, and antiviral activities. The crystal structure of recombinant human EDN, in the unliganded form has been determined previously (Mosimann, S. C., Newton, D. L., Youle, R. J., and James, M. N. G. (1996) J. Mol. Biol. 260, 540-552). We have now determined high resolution (1.8 A) crystal, structures for EDN in complex with adenosine-3',5'-diphosphate, (3',5'-ADP), adenosine-2',5'-di-phosphate (2',5'-ADP), adenosine-5'-diphosphate (5'-ADP) as well as for a native structure in the, presence of sulfate refined at 1.6 A. The inhibition constant of these, mononucleotides for EDN has been determined. The structures present the, first detailed picture of differences between EDN and RNase A in substrate, recognition at the ribonucleolytic active site. They also provide a, starting point for the design of tight-binding inhibitors, which may be, used to restrain the RNase activity of EDN.
Disease
Known diseases associated with this structure: Central hypoventilation syndrome, congenital OMIM:[131242], Hirschsprung disease OMIM:[131242], Shah-Waardenburg syndrome OMIM:[131242]
About this Structure
1HI4 is a Single protein structure of sequence from Homo sapiens with A3P as ligand. Active as Pancreatic ribonuclease, with EC number 3.1.27.5 Structure known Active Site: A3P. Full crystallographic information is available from OCA.
Reference
Mapping the ribonucleolytic active site of eosinophil-derived neurotoxin (EDN). High resolution crystal structures of EDN complexes with adenylic nucleotide inhibitors., Leonidas DD, Boix E, Prill R, Suzuki M, Turton R, Minson K, Swaminathan GJ, Youle RJ, Acharya KR, J Biol Chem. 2001 May 4;276(18):15009-17. Epub 2001 Jan 11. PMID:11154698
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