3FMR

Crystal structure of an Encephalitozoon cuniculi methionine aminopeptidase type 2 with angiogenesis inhibitor TNP470 bound

Replaces:  3D0D

Summary for 3FMR

• Entry DOI: 10.2210/pdb3fmr/pdb
• Related: 3FM3 3FMQ
• Descriptor: Methionine aminopeptidase 2, FE (III) ION, (1R,2S,3S,4R)-4-hydroxy-2-methoxy-4-methyl-3-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]cyclohexyl (chloroacetyl)carbamate, ... (5 entities in total)
• Functional Keywords: methionine aminopeptidase type2, metap2, metap2 tnp470 complex, encephalitozoon cuniculi, structural genomics, psi-2, protein structure initiative, new york sgx research center for structural genomics, nysgxrc, aminopeptidase, cobalt, hydrolase, metal-binding, protease
• Biological source: Encephalitozoon cuniculi
• Total number of polymer chains: 2
• Total formula weight: 81474.30

Authors

Alvarado, J.J.,Russell, M.,Zhang, A.,Adams, J.,Toro, R.,Burley, S.K.,Weiss, L.M.,Almo, S.C.,New York SGX Research Center for Structural Genomics (NYSGXRC) (deposition date: 2008-12-22, release date: 2009-01-13, Last modification date: 2024-10-09)

Primary citation

Alvarado, J.J.,Nemkal, A.,Sauder, J.M.,Russell, M.,Akiyoshi, D.E.,Shi, W.,Almo, S.C.,Weiss, L.M.
Structure of a microsporidian methionine aminopeptidase type 2 complexed with fumagillin and TNP-470.
Mol.Biochem.Parasitol., 168:158-167, 2009

PubMed Abstract: Microsporidia are protists that have been reported to cause infections in both vertebrates and invertebrates. They have emerged as human pathogens particularly in patients that are immunosuppressed and cases of gastrointestinal infection, encephalitis, keratitis, sinusitis, myositis and disseminated infection are well described in the literature. While benzimidazoles are active against many species of microsporidia, these drugs do not have significant activity against Enterocytozoon bieneusi. Fumagillin and its analogues have been demonstrated to have activity invitro and in animal models of microsporidiosis and human infections due to E. bieneusi. Fumagillin and its analogues inhibit methionine aminopeptidase type 2. Encephalitozoon cuniculi MetAP2 (EcMetAP2) was cloned and expressed as an active enzyme using a baculovirus system. The crystal structure of EcMetAP2 was determined with and without the bound inhibitors fumagillin and TNP-470. This structure classifies EcMetAP2 as a member of the MetAP2c family. The EcMetAP2 structure was used to generate a homology model of the E. bieneusi MetAP2. Comparison of microsporidian MetAP2 structures with human MetAP2 provides insights into the design of inhibitors that might exhibit specificity for microsporidian MetAP2.

PubMed: 19660503
DOI: 10.1016/j.molbiopara.2009.07.008

Experimental method

X-RAY DIFFRACTION (2.89 Å)