2g71: Difference between revisions

Revision as of 15:02, 28 July 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:2g71.png

Template:STRUCTURE 2g71

Structure of hPNMT with inhibitor 3-fluoromethyl-7-trifluoropropyl-THIQ and AdoHcyStructure of hPNMT with inhibitor 3-fluoromethyl-7-trifluoropropyl-THIQ and AdoHcy

Template:ABSTRACT PUBMED 17845018

About this StructureAbout this Structure

2G71 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Enzyme adaptation to inhibitor binding: a cryptic binding site in phenylethanolamine N-methyltransferase., Gee CL, Drinkwater N, Tyndall JD, Grunewald GL, Wu Q, McLeish MJ, Martin JL, J Med Chem. 2007 Oct 4;50(20):4845-53. Epub 2007 Sep 11. PMID:17845018

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-'''Structure of hPNMT with inhibitor 3-fluoromethyl-7-trifluoropropyl-THIQ and AdoHcy'''
+===Structure of hPNMT with inhibitor 3-fluoromethyl-7-trifluoropropyl-THIQ and AdoHcy===
-==Overview==
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-Shape complementarity is a fundamental principle of inhibitor design. Here we show that an enzyme for which the crystal structure has been determined (phenylethanolamine N-methyltransferase, PNMT) conceals a cryptic binding site. This site is revealed upon binding of inhibitors that are double the size of the physiological substrate. These large inhibitors are not predicted to bind in that they protrude through the accessible surface calculated from a PNMT/7-aminosulfonyl-1,2,3,4-tetrahydroisoquinoline (SK&amp;F 29661) crystal structure, yet they are potent inhibitors of PNMT. We determined structures of the enzyme complexed with large inhibitors and found that the volume of the active site increases by 140 A3 upon binding. Changes in active site size and shape are brought about by unfavorable side chain conformations and rigid body helix motions. The energetic cost is modest, estimated at 2-3 kcal/mol from mutational analyses. Our findings further underline the importance of protein flexibility in structure-based inhibitor design studies.
+The line below this paragraph, {{ABSTRACT_PUBMED_17845018}}, adds the Publication Abstract to the page
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 ==About this Structure==
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 [[Category: Tyndall, J D.A.]]
 [[Category: Methyltransferase]]
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