4U69
HsMetAP complex with (1-amino-2-methylpentyl)phosphonic acid
Summary for 4U69
| Entry DOI | 10.2210/pdb4u69/pdb |
| Related | 4U1B 4U6C 4U6E 4u6j 4u6w 4u6z 4u70 4u71 4u73 4u75 4u76 |
| Descriptor | Methionine aminopeptidase 1, COBALT (II) ION, POTASSIUM ION, ... (5 entities in total) |
| Functional Keywords | hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 34792.34 |
| Authors | Arya, T.,Addlagatta, A. (deposition date: 2014-07-28, release date: 2015-03-25, Last modification date: 2024-03-20) |
| Primary citation | Arya, T.,Reddi, R.,Kishor, C.,Ganji, R.J.,Bhukya, S.,Gumpena, R.,McGowan, S.,Drag, M.,Addlagatta, A. Identification of the Molecular Basis of Inhibitor Selectivity between the Human and Streptococcal Type I Methionine Aminopeptidases J.Med.Chem., 58:2350-2357, 2015 Cited by PubMed Abstract: The methionine aminopeptidase (MetAP) family is responsible for the cleavage of the initiator methionine from newly synthesized proteins. Currently, there are no small molecule inhibitors that show selectivity toward the bacterial MetAPs compared to the human enzyme. In our current study, we have screened 20 α-aminophosphonate derivatives and identified a molecule (compound 15) that selectively inhibits the S. pneumonia MetAP in low micromolar range but not the human enzyme. Further bioinformatics, biochemical, and structural analyses suggested that phenylalanine (F309) in the human enzyme and methionine (M205) in the S. pneumonia MetAP at the analogous position render them with different susceptibilities against the identified inhibitor. X-ray crystal structures of various inhibitors in complex with wild type and F309M enzyme further established the molecular basis for the inhibitor selectivity. PubMed: 25699713DOI: 10.1021/jm501790e PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
Download full validation report
