1ORE

Human Adenine Phosphoribosyltransferase

1ORE の概要

• エントリーDOI: 10.2210/pdb1ore/pdb
• 分子名称: Adenine phosphoribosyltransferase, CHLORIDE ION, ADENOSINE MONOPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: human adenine phosphoribosyltransferase, leishmaniasis, urolithiasis, glycosyl transferase, 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: 1
• 化学式量合計: 20012.40

構造登録者

Thiemann, O.H.,Silva, M.,Oliva, G.,Silva, C.H.T.P.,Iulek, J. (登録日: 2003-03-12, 公開日: 2004-03-30, 最終更新日: 2024-02-14)

主引用文献

Silva, M.,Silva, C.H.T.P.,Iulek, J.,Thiemann, O.H.
Three-dimensional structure of human adenine phosphoribosyltransferase and its relation to DHA-urolithiasis.
Biochemistry, 43:7663-7671, 2004

PubMed Abstract: In mammals, adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) is present in all tissues and provides the only known mechanism for the metabolic salvage of adenine resulting from the polyamine biosynthesis pathway or from dietary sources. In humans, APRT deficiency results in serious kidney illness such as nephrolithiasis, interstitial nephritis, and chronic renal failure as a result of 2,8-dihydroxyadenine (DHA) precipitation in the renal interstitium. To address the molecular basis of DHA-urolithiasis, the recombinant human APRT was crystallized in complex with adenosine 5'-monophosphate (AMP). Refinement of X-ray diffraction data extended to 2.1 A resolution led to a final crystallographic R(factor) of 13.3% and an R(free) of 17.6%. This structure is composed of nine beta-strands and six alpha-helices, and the active site pocket opens slightly to accommodate the AMP product. The core of APRT is similar to that of other phosphoribosyltransferases (PRTases), although the adenine-binding domain is quite different. Structural comparisons between the human APRT and other "type I" PRTases of known structure revealed several important features of the biochemistry of PRTases. We propose that the residues located at positions corresponding to Leu159 and Ala131 in hAPRT are responsible for the base specificities of type I PRTases. The comparative analysis shown here also provides structural information for the mechanism by which mutations in the human APRT lead to DHA-urolithiasis.

PubMed: 15196008
DOI: 10.1021/bi0360758

実験手法

X-RAY DIFFRACTION (2.1 Å)