|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5392
|
|
pubmed:dateCreated |
1998-12-1
|
|
pubmed:databankReference |
|
|
pubmed:abstractText |
The fungal metabolite fumagillin suppresses the formation of new blood vessels, and a fumagillin analog is currently in clinical trials as an anticancer agent. The molecular target of fumagillin is methionine aminopeptidase-2 (MetAP-2). A 1.8 A resolution crystal structure of free and inhibited human MetAP-2 shows a covalent bond formed between a reactive epoxide of fumagillin and histidine-231 in the active site of MetAP-2. Extensive hydrophobic and water-mediated polar interactions with other parts of fumagillin provide additional affinity. Fumagillin-based drugs inhibit MetAP-2 but not MetAP-1, and the three-dimensional structure also indicates the likely determinants of this specificity. The structural basis for fumagillin's potency and specificity forms the starting point for structure-based drug design.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Nov
|
|
pubmed:issn |
0036-8075
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
13
|
|
pubmed:volume |
282
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1324-7
|
|
pubmed:dateRevised |
2007-11-14
|
|
pubmed:meshHeading |
pubmed-meshheading:9812898-Amino Acid Sequence,
pubmed-meshheading:9812898-Aminopeptidases,
pubmed-meshheading:9812898-Binding Sites,
pubmed-meshheading:9812898-Crystallography, X-Ray,
pubmed-meshheading:9812898-Cyclohexanes,
pubmed-meshheading:9812898-Fatty Acids, Unsaturated,
pubmed-meshheading:9812898-Humans,
pubmed-meshheading:9812898-Hydrogen Bonding,
pubmed-meshheading:9812898-Metalloendopeptidases,
pubmed-meshheading:9812898-Models, Molecular,
pubmed-meshheading:9812898-Molecular Sequence Data,
pubmed-meshheading:9812898-Protein Conformation,
pubmed-meshheading:9812898-Protein Structure, Secondary,
pubmed-meshheading:9812898-Sequence Alignment,
pubmed-meshheading:9812898-Sesquiterpenes
|
|
pubmed:year |
1998
|
|
pubmed:articleTitle |
Structure of human methionine aminopeptidase-2 complexed with fumagillin.
|
|
pubmed:affiliation |
J. Clardy, Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, NY 14853-1301, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
