2R8Q

Structure of LmjPDEB1 in complex with IBMX

2R8Q の概要

• エントリーDOI: 10.2210/pdb2r8q/pdb
• 分子名称: Class I phosphodiesterase PDEB1, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: leishimaniasis, parasite inhibitor selectivity, camp phosphodiesterase, hydrolase
• 由来する生物種: Leishmania major
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 81751.76

構造登録者

Wang, H.,Yan, Z.,Geng, J.,Kunz, S.,Seebeck, T.,Ke, H. (登録日: 2007-09-11, 公開日: 2007-12-18, 最終更新日: 2024-04-03)

主引用文献

Wang, H.,Yan, Z.,Geng, J.,Kunz, S.,Seebeck, T.,Ke, H.
Crystal structure of the Leishmania major phosphodiesterase LmjPDEB1 and insight into the design of the parasite-selective inhibitors.
Mol.Microbiol., 66:1029-1038, 2007

PubMed Abstract: Human leishmaniasis is a major public health problem in many countries, but chemotherapy is in an unsatisfactory state. Leishmania major phosphodiesterases (LmjPDEs) have been shown to play important roles in cell proliferation and apoptosis of the parasite. Thus LmjPDE inhibitors may potentially represent a novel class of drugs for the treatment of leishmaniasis. Reported here are the kinetic characterization of the LmjPDEB1 catalytic domain and its crystal structure as a complex with 3-isobutyl-1-methylxanthine (IBMX) at 1.55 A resolution. The structure of LmjPDEB1 is similar to that of human PDEs. IBMX stacks against the conserved phenylalanine and forms a hydrogen bond with the invariant glutamine, in a pattern common to most inhibitors bound to human PDEs. However, an extensive structural comparison reveals subtle, but significant differences between the active sites of LmjPDEB1 and human PDEs. In addition, a pocket next to the inhibitor binding site is found to be unique to LmjPDEB1. This pocket is isolated by two gating residues in human PDE families, but constitutes a natural expansion of the inhibitor binding pocket in LmjPDEB1. The structure particularity might be useful for the development of parasite-selective inhibitors for the treatment of leishmaniasis.

PubMed: 17944832
DOI: 10.1111/j.1365-2958.2007.05976.x

実験手法

X-RAY DIFFRACTION (1.5 Å)