6LZC
crystal structure of Human Methionine aminopeptidase (HsMetAP1b) in complex with KV-P2-4H-05
Summary for 6LZC
| Entry DOI | 10.2210/pdb6lzc/pdb |
| Descriptor | Methionine aminopeptidase 1, COBALT (II) ION, ~{N}-oxidanyl-1-(phenylmethyl)pyrrolo[2,3-b]pyridine-4-carboxamide, ... (7 entities in total) |
| Functional Keywords | methionine aminopeptidase, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 37644.65 |
| Authors | Sandeep, C.B.,Addlagatta, A. (deposition date: 2020-02-18, release date: 2021-02-24, Last modification date: 2023-11-29) |
| Primary citation | Bala, S.,Yellamanda, K.V.,Kadari, A.,Ravinuthala, V.S.U.,Kattula, B.,Singh, O.V.,Gundla, R.,Addlagatta, A. Selective inhibition of Helicobacter pylori methionine aminopeptidase by azaindole hydroxamic acid derivatives: Design, synthesis, in vitro biochemical and structural studies. Bioorg.Chem., 115:105185-105185, 2021 Cited by PubMed Abstract: Methionine aminopeptidases (MetAPs) are an important class of enzymes that work co-translationally for the removal of initiator methionine. Chemical inhibition or gene knockdown is lethal to the microbes suggesting that they can be used as antibiotic targets. However, sequence and structural similarity between the microbial and host MetAPs has been a challenge in the identification of selective inhibitors. In this study, we have analyzed several thousands of MetAP sequences and established a pattern of variation in the S1 pocket of the enzyme. Based on this knowledge, we have designed a library of 17 azaindole based hydroxamic acid derivatives which selectively inhibited the MetAP from H. pylori compared to the human counterpart. Structural studies provided the molecular basis for the selectivity. PubMed: 34329997DOI: 10.1016/j.bioorg.2021.105185 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.35 Å) |
Structure validation
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