6LZC

crystal structure of Human Methionine aminopeptidase (HsMetAP1b) in complex with KV-P2-4H-05

6LZC の概要

• エントリーDOI: 10.2210/pdb6lzc/pdb
• 分子名称: Methionine aminopeptidase 1, COBALT (II) ION, ~{N}-oxidanyl-1-(phenylmethyl)pyrrolo[2,3-b]pyridine-4-carboxamide, ... (7 entities in total)
• 機能のキーワード: methionine aminopeptidase, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37644.65

構造登録者

Sandeep, C.B.,Addlagatta, A. (登録日: 2020-02-18, 公開日: 2021-02-24, 最終更新日: 2023-11-29)

主引用文献

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

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: 34329997
DOI: 10.1016/j.bioorg.2021.105185

実験手法

X-RAY DIFFRACTION (1.35 Å)