3HIV

Crystal structure of Saporin-L1 in complex with the trinucleotide inhibitor, a transition state analogue

3HIV の概要

• エントリーDOI: 10.2210/pdb3hiv/pdb
• 関連するPDBエントリー: 3HIO 3HIQ 3HIS 3HIT 3HIW
• 分子名称: Vacuolar saporin, (2R,3R,4R,5R)-5-(2-amino-6-oxo-3,6-dihydro-9H-purin-9-yl)-2-({[(S)-({(3R,4R)-4-({[(S)-{[(2R,3R,4R,5R)-5-(2-amino-6-oxo-6,8-dihydro-9H-purin-9-yl)-2-(hydroxymethyl)-4-methoxytetrahydrofuran-3-yl]oxy}(hydroxy)phosphoryl]oxy}methyl)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]pyrrolidin-3-yl}oxy)(hydroxy)phosphoryl]oxy}methyl)-4-methoxytetrahydrofuran-3-yl 3-hydroxypropyl hydrogen (S)-phosphate (3 entities in total)
• 機能のキーワード: transition state, ribosome inactivating proteins, rips, hydrolase, plant defense, protein synthesis inhibitor, toxin, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Saponaria officinalis (Common soapwort)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59775.18

構造登録者

Ho, M.,Sturm, M.B.,Almo, S.C.,Schramm, V.L. (登録日: 2009-05-20, 公開日: 2009-12-08, 最終更新日: 2024-02-21)

主引用文献

Ho, M.C.,Sturm, M.B.,Almo, S.C.,Schramm, V.L.
Transition state analogues in structures of ricin and saporin ribosome-inactivating proteins.
Proc.Natl.Acad.Sci.USA, 106:20276-20281, 2009

PubMed Abstract: Ricin A-chain (RTA) and saporin-L1 (SAP) catalyze adenosine depurination of 28S rRNA to inhibit protein synthesis and cause cell death. We present the crystal structures of RTA and SAP in complex with transition state analogue inhibitors. These tight-binding inhibitors mimic the sarcin-ricin recognition loop of 28S rRNA and the dissociative ribocation transition state established for RTA catalysis. RTA and SAP share unique purine-binding geometry with quadruple pi-stacking interactions between adjacent adenine and guanine bases and 2 conserved tyrosines. An arginine at one end of the pi-stack provides cationic polarization and enhanced leaving group ability to the susceptible adenine. Common features of these ribosome-inactivating proteins include adenine leaving group activation, a remarkable lack of ribocation stabilization, and conserved glutamates as general bases for activation of the H(2)O nucleophile. Catalytic forces originate primarily from leaving group activation evident in both RTA and SAP in complex with transition state analogues.

PubMed: 19920175
DOI: 10.1073/pnas.0911606106

実験手法

X-RAY DIFFRACTION (2.14 Å)