4FLJ

Human MetAP1 with bengamide analog Y08, in Mn form

Summary for 4FLJ

• Entry DOI: 10.2210/pdb4flj/pdb
• Related: 3PKA 3PKB 3PKC 3PKD 3PKE 4FLI 4FLK 4FLL
• Descriptor: Methionine aminopeptidase 1, MANGANESE (II) ION, (E,2R,3R,4S,5R)-N-[[(3S)-1-cyclopropylcarbonylpiperidin-3-yl]methyl]-2-methoxy-8,8-dimethyl-3,4,5-tris(oxidanyl)non-6-enamide, ... (5 entities in total)
• Functional Keywords: hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P53582
• Total number of polymer chains: 1
• Total formula weight: 37404.30

Authors

Ye, Q.Z.,Xu, W. (deposition date: 2012-06-14, release date: 2012-09-19, Last modification date: 2024-02-28)

Primary citation

Xu, W.,Lu, J.P.,Ye, Q.Z.
Structural analysis of bengamide derivatives as inhibitors of methionine aminopeptidases.
J.Med.Chem., 55:8021-8027, 2012

PubMed Abstract: Natural-product-derived bengamides possess potent antiproliferative activity and target human methionine aminopeptidases (MetAPs) for their cellular effects. Several derivatives were designed, synthesized, and evaluated as MetAP inhibitors. Here, we present four new X-ray structures of human MetAP1 in complex with the inhibitors. Together with the previous structures of bengamide derivatives with human MetAP2 and tubercular MtMetAP1c, analysis of the interactions of these inhibitors at the active site provides structural basis for further modification of these bengamide inhibitors for improved potency and selectivity as anticancer and antibacterial therapeutics.

PubMed: 22913487
DOI: 10.1021/jm3008695

Experimental method

X-RAY DIFFRACTION (1.74 Å)