1YRY

Crystal structure of human PNP complexed with MESG

1YRY の概要

• エントリーDOI: 10.2210/pdb1yry/pdb
• 分子名称: Purine nucleoside phosphorylase, SULFATE ION, 7-METHYL-6-THIO-GUANOSINE, ... (4 entities in total)
• 機能のキーワード: purine nucleoside phosphorylase, drug design, synchrotron, mesg, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton (By similarity): P00491
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32786.40

構造登録者

Silva, R.G.,Pereira, J.H.,Canduri, F.,Basso, L.A.,de Azevedo Jr., W.F.,Santos, D.S. (登録日: 2005-02-05, 公開日: 2006-01-17, 最終更新日: 2023-10-25)

主引用文献

Silva, R.G.,Pereira, J.H.,Canduri, F.,de Azevedo Jr., W.F.,Basso, L.A.,Santos, D.S.
Kinetics and crystal structure of human purine nucleoside phosphorylase in complex with 7-methyl-6-thio-guanosine
Arch.Biochem.Biophys., 442:49-58, 2005

PubMed Abstract: Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and drugs that inhibit this enzyme may have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Here, we describe kinetics and crystal structure of human PNP in complex with 7-methyl-6-thio-guanosine, a synthetic substrate, which is largely used in activity assays. Analysis of the structure identifies different protein conformational changes upon ligand binding, and comparison of kinetic and structural data permits an understanding of the effects of atomic substitution on key positions of the synthetic substrate and their consequences to enzyme binding and catalysis. Such knowledge may be helpful in designing new PNP inhibitors.

PubMed: 16154528
DOI: 10.1016/j.abb.2005.07.021

実験手法

X-RAY DIFFRACTION (2.8 Å)