2bb7: Difference between revisions

Revision as of 20:03, 3 May 2008

Mn Form Of E. coli Methionine Aminopeptidase In Complex With a quinolinyl sulfonamide inhibitor

OverviewOverview

Quinolinyl sulfonamides, such as N-(quinolin-8-yl)methanesulfonamide (10) and N-(5-chloroquinolin-8-yl)methanesulfonamide (11), were identified as potent methionine aminopeptidase (MetAP) inhibitors by high throughput screening of a diverse chemical library of small organic compounds. They showed different inhibitory potencies on Co(II)-, Ni(II)-, Fe(II)-, Mn(II)-, and Zn(II)-forms of Escherichia coli MetAP, and their inhibition is dependent on metal concentration. X-ray structures of E. coli MetAP complexed with 10 revealed that the inhibitor forms a metal complex with the residue H79 at the enzyme active site; the complex is further stabilized by an extended H-bond and metal interaction network. Analysis of the inhibition of MetAP by these inhibitors indicates that this is a typical mechanism of inhibition for many non-peptidic MetAP inhibitors and emphasizes the importance of defining in vitro conditions for identifying and evaluating MetAP inhibitors that will be capable of giving information relevant to the in vivo situation.

About this StructureAbout this Structure

2BB7 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

Metal mediated inhibition of methionine aminopeptidase by quinolinyl sulfonamides., Huang M, Xie SX, Ma ZQ, Hanzlik RP, Ye QZ, Biochem Biophys Res Commun. 2006 Jan 13;339(2):506-13. Epub 2005 Nov 15. PMID:16300729 Page seeded by OCA on Sat May 3 20:03:53 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2bb7.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2bb7 |SIZE=350|CAPTION= <scene name='initialview01'>2bb7</scene>, resolution 1.700&Aring;
+The line below this paragraph, containing "STRUCTURE_2bb7", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=QMS:N-(QUINOLIN-8-YL)METHANESULFONAMIDE'>QMS</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionyl_aminopeptidase Methionyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.18 3.4.11.18] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= map ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
+-->
-|DOMAIN=
+{{STRUCTURE_2bb7|  PDB=2bb7  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bb7 OCA], [http://www.ebi.ac.uk/pdbsum/2bb7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2bb7 RCSB]</span>
-}}
 '''Mn Form Of E. coli Methionine Aminopeptidase In Complex With a quinolinyl sulfonamide inhibitor'''
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 [[Category: Single protein]]
 [[Category: Ye, Q Z.]]
-[[Category: enzyme-inhibitor complex]]
+[[Category: Enzyme-inhibitor complex]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: metalloenzyme]]
+[[Category: Metalloenzyme]]
-[[Category: mn(ii)-form]]
+[[Category: Trimetallic]]
-[[Category: trimetallic]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 20:03:53 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:03:49 2008''