1ZN8

Human Adenine Phosphoribosyltransferase Complexed with AMP, in Space Group P1 at 1.76 A Resolution

1ZN8 の概要

• エントリーDOI: 10.2210/pdb1zn8/pdb
• 関連するPDBエントリー: 1ORE 1ZN7 1ZN9
• 分子名称: Adenine phosphoribosyltransferase, ADENOSINE MONOPHOSPHATE, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: glycosyltransferase, purine salvage, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P07741
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39989.35

構造登録者

Iulek, J.,Silva, M.,Tomich, C.H.T.P.,Thiemann, O.H. (登録日: 2005-05-11, 公開日: 2006-04-25, 最終更新日: 2024-02-14)

主引用文献

Silva, C.H.,Silva, M.,Iulek, J.,Thiemann, O.H.
Structural Complexes of Human Adenine Phosphoribosyltransferase Reveal Novel Features of the APRT Catalytic Mechanism
J.Biomol.Struct.Dyn., 25:589-598, 2008

PubMed Abstract: Adenine phosphoribosyltransferase (APRT) is an important enzyme component of the purine recycling pathway. Parasitic protozoa of the order Kinetoplastida are unable to synthesize purines de novo and use the salvage pathway for the synthesis of purine bases rendering this biosynthetic pathway an attractive target for antiparasitic drug design. The recombinant human adenine phosphoribosyltransferase (hAPRT) structure was resolved in the presence of AMP in the active site to 1.76 A resolution and with the substrates PRPP and adenine simultaneously bound to the catalytic site to 1.83 A resolution. An additional structure was solved containing one subunit of the dimer in the apo-form to 2.10 A resolution. Comparisons of these three hAPRT structures with other 'type I' PRTases revealed several important features of this class of enzymes. Our data indicate that the flexible loop structure adopts an open conformation before and after binding of both substrates adenine and PRPP. Comparative analyses presented here provide structural evidence to propose the role of Glu104 as the residue that abstracts the proton of adenine N9 atom before its nucleophilic attack on the PRPP anomeric carbon. This work leads to new insights to the understanding of the APRT catalytic mechanism.

PubMed: 18399692

実験手法

X-RAY DIFFRACTION (1.76 Å)