4LDR

Structure of the S283Y mutant of MRDI

4LDR の概要

• エントリーDOI: 10.2210/pdb4ldr/pdb
• 関連するPDBエントリー: 4LDQ
• 分子名称: Methylthioribose-1-phosphate isomerase (2 entities in total)
• 機能のキーワード: helix bundle, rossmann-like fold, isomerase, cell invasion
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : Q9BV20
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 78541.57

構造登録者

Sousa, M.C.,Templeton, P.D.,Metzner, S.I. (登録日: 2013-06-25, 公開日: 2013-07-31, 最終更新日: 2024-02-28)

主引用文献

Templeton, P.D.,Litman, E.S.,Metzner, S.I.,Ahn, N.G.,Sousa, M.C.
Structure of Mediator of RhoA-Dependent Invasion (MRDI) Explains Its Dual Function as a Metabolic Enzyme and a Mediator of Cell Invasion.
Biochemistry, 52:5675-5684, 2013

PubMed Abstract: Metastatic melanoma is among the most intractable cancers to treat; patients show resistance to therapy and limited survival time. A critical step in the development of metastatic melanoma is the acquisition of invasion and transition from thin to thick tumors on the skin, followed by invasion to lymph nodes. Prior studies have shown that metastatic melanoma is associated with dysregulation of RhoA and enhanced expression of a protein named "mediator of RhoA-dependent invasion (MRDI)". Importantly, MRDI is a "moonlighting" enzyme, with two distinct functions in melanoma cells. First, MRDI acts as a methylthioribose-1-phosphate (MTR-1-P) isomerase, catalyzing a critical step in methionine salvage. Second, MRDI promotes and is necessary for melanoma cell invasion, independent of its catalytic activity. This paper demonstrates that MtnA, a bacterial MTR-1-P isomerase, rescues the methionine salvage function of MRDI, but is unable to rescue its role in invasion. The crystal structure of MRDI was solved to a resolution of 2.5 Å to identify structural elements important for its invasion activity. This structure and its comparison with other MTR-1-P isomerases are presented, and mutations within a region separate from the MTR-1-P binding site, which interfere with invasion, are identified. Thus, structural elements in MRDI distal from the MTR-1-P catalytic site are responsible for the invasion phenotype.

PubMed: 23859498
DOI: 10.1021/bi400556e

実験手法

X-RAY DIFFRACTION (2.292 Å)