2BB7

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

Summary for 2BB7

• Entry DOI: 10.2210/pdb2bb7/pdb
• Descriptor: Methionine aminopeptidase, MANGANESE (II) ION, SODIUM ION, ... (5 entities in total)
• Functional Keywords: trimetallic, mn(ii)-form, hydrolase, enzyme-inhibitor complex, metalloenzyme
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 29780.91

Authors

Ye, Q.Z. (deposition date: 2005-10-17, release date: 2006-01-24, Last modification date: 2023-08-23)

Primary citation

Huang, M.,Xie, S.X.,Ma, Z.Q.,Hanzlik, R.P.,Ye, Q.Z.
Metal mediated inhibition of methionine aminopeptidase by quinolinyl sulfonamides
Biochem.Biophys.Res.Commun., 339:506-513, 2006

PubMed Abstract: 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.

PubMed: 16300729
DOI: 10.1016/j.bbrc.2005.11.042

Experimental method

X-RAY DIFFRACTION (1.7 Å)