1n7j
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1n7j |SIZE=350|CAPTION= <scene name='initialview01'>1n7j</scene>, resolution 2.70Å | |PDB= 1n7j |SIZE=350|CAPTION= <scene name='initialview01'>1n7j</scene>, resolution 2.70Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=IDI:7-IODO-1,2,3,4-TETRAHYDRO-ISOQUINOLINE'>IDI</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Phenylethanolamine_N-methyltransferase Phenylethanolamine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.28 2.1.1.28] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Phenylethanolamine_N-methyltransferase Phenylethanolamine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.28 2.1.1.28] </span> |
|GENE= PNMT OR PENT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= PNMT OR PENT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1hnn|1HNN]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1n7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n7j OCA], [http://www.ebi.ac.uk/pdbsum/1n7j PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1n7j RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
The crystal structures of human phenylethanolamine N-methyltransferase in complex with S-adenosyl-l-homocysteine (7, AdoHcy) and either 7-iodo-1,2,3,4-tetrahydroisoquinoline (2) or 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine (3, LY134046) were determined and compared with the structure of the enzyme complex with 7 and 7-aminosulfonyl-1,2,3,4-tetrahydroisoquinoline (1, SK&F 29661). The enzyme is able to accommodate a variety of chemically disparate functional groups on the aromatic ring of the inhibitors through adaptation of the binding pocket for this substituent and by subtle adjustments of the orientation of the inhibitors within the relatively planar binding site. In addition, the interactions formed by the amine nitrogen of all three inhibitors reinforce the hypothesis that this functional group mimics the beta-hydroxyl of norepinephrine rather than the amine. These studies provide further clues for the development of improved inhibitors for use as pharmacological probes. | The crystal structures of human phenylethanolamine N-methyltransferase in complex with S-adenosyl-l-homocysteine (7, AdoHcy) and either 7-iodo-1,2,3,4-tetrahydroisoquinoline (2) or 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine (3, LY134046) were determined and compared with the structure of the enzyme complex with 7 and 7-aminosulfonyl-1,2,3,4-tetrahydroisoquinoline (1, SK&F 29661). The enzyme is able to accommodate a variety of chemically disparate functional groups on the aromatic ring of the inhibitors through adaptation of the binding pocket for this substituent and by subtle adjustments of the orientation of the inhibitors within the relatively planar binding site. In addition, the interactions formed by the amine nitrogen of all three inhibitors reinforce the hypothesis that this functional group mimics the beta-hydroxyl of norepinephrine rather than the amine. These studies provide further clues for the development of improved inhibitors for use as pharmacological probes. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Hypertension, essential, 145500 (1) OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=171190 171190]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 33: | Line 33: | ||
[[Category: McLeish, M J.]] | [[Category: McLeish, M J.]] | ||
[[Category: McMillan, F M.]] | [[Category: McMillan, F M.]] | ||
| - | [[Category: IDI]] | ||
| - | [[Category: SAH]] | ||
[[Category: adrenaline]] | [[Category: adrenaline]] | ||
[[Category: catecholamine]] | [[Category: catecholamine]] | ||
| Line 42: | Line 40: | ||
[[Category: s-adenosylmethionine]] | [[Category: s-adenosylmethionine]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:26:27 2008'' |
Revision as of 19:26, 30 March 2008
| |||||||
| , resolution 2.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | PNMT OR PENT (Homo sapiens) | ||||||
| Activity: | Phenylethanolamine N-methyltransferase, with EC number 2.1.1.28 | ||||||
| Related: | 1HNN
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
The structure of Phenylethanolamine N-methyltransferase in complex with S-adenosylhomocysteine and an iodinated inhibitor
Overview
The crystal structures of human phenylethanolamine N-methyltransferase in complex with S-adenosyl-l-homocysteine (7, AdoHcy) and either 7-iodo-1,2,3,4-tetrahydroisoquinoline (2) or 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine (3, LY134046) were determined and compared with the structure of the enzyme complex with 7 and 7-aminosulfonyl-1,2,3,4-tetrahydroisoquinoline (1, SK&F 29661). The enzyme is able to accommodate a variety of chemically disparate functional groups on the aromatic ring of the inhibitors through adaptation of the binding pocket for this substituent and by subtle adjustments of the orientation of the inhibitors within the relatively planar binding site. In addition, the interactions formed by the amine nitrogen of all three inhibitors reinforce the hypothesis that this functional group mimics the beta-hydroxyl of norepinephrine rather than the amine. These studies provide further clues for the development of improved inhibitors for use as pharmacological probes.
About this Structure
1N7J is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Molecular recognition of sub-micromolar inhibitors by the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase., McMillan FM, Archbold J, McLeish MJ, Caine JM, Criscione KR, Grunewald GL, Martin JL, J Med Chem. 2004 Jan 1;47(1):37-44. PMID:14695818
Page seeded by OCA on Sun Mar 30 22:26:27 2008
Categories: Homo sapiens | Phenylethanolamine N-methyltransferase | Single protein | Archbold, J. | Caine, J M. | Criscione, K R. | Grunewald, G L. | Martin, J L. | McLeish, M J. | McMillan, F M. | Adrenaline | Catecholamine | Epinephrine | Methyltransferase | S-adenolsylhomocysteine | S-adenosylmethionine
