4GPL

Structure of Cbl(TKB) bound to a phosphorylated pentapeptide

4GPL の概要

• エントリーDOI: 10.2210/pdb4gpl/pdb
• 分子名称: ACE-PTR-THR-PRO-GLU-PRO, PEPTIDE INHIBITOR, E3 ubiquitin-protein ligase CBL (3 entities in total)
• 機能のキーワード: ubiquitin ligase(e3), ligase-ligase inhibitor complex, ligase/ligase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P22681
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36553.10

構造登録者

Borgstahl, G.,Natarajan, A. (登録日: 2012-08-21, 公開日: 2013-09-18, 最終更新日: 2024-10-30)

主引用文献

Kumar, E.A.,Chen, Q.,Kizhake, S.,Kolar, C.,Kang, M.,Chang, C.E.,Borgstahl, G.E.,Natarajan, A.
The paradox of conformational constraint in the design of Cbl(TKB)-binding peptides.
Sci Rep, 3:1639-1639, 2013

PubMed Abstract: Solving the crystal structure of Cbl(TKB) in complex with a pentapeptide, pYTPEP, revealed that the PEP region adopted a poly-L-proline type II (PPII) helix. An unnatural amino acid termed a proline-templated glutamic acid (ptE) that constrained both the backbone and sidechain to the bound conformation was synthesized and incorporated into the pYTPXP peptide. We estimated imposing structural constraints onto the backbone and sidechain of the peptide and preorganize it to the bound conformation in solution will yield nearly an order of magnitude improvement in activity. NMR studies confirmed that the ptE-containing peptide adopts the PPII conformation, however, competitive binding studies showed an order of magnitude loss of activity. Given the emphasis that is placed on imposing structural constraints, we provide an example to support the contrary. These results point to conformational flexibility at the interface, which have implications in the design of potent Cbl(TKB)-binding peptides.

PubMed: 23572190
DOI: 10.1038/srep01639

実験手法

X-RAY DIFFRACTION (3 Å)