6MXC

Crystal structure of Trypanosoma brucei hypoxanthine-guanine-xanthine phosphoribosyltranferase in complex with GMP

6MXC の概要

• エントリーDOI: 10.2210/pdb6mxc/pdb
• 関連するPDBエントリー: 6MXB
• 分子名称: Hypoxanthine-guanine phosphoribosyltransferase, GUANOSINE-5'-MONOPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: 6-oxopurine prts, trypanosoma brucei, purine salvage, transferase
• 由来する生物種: Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 186280.67

構造登録者

Teran, D.,Guddat, L. (登録日: 2018-10-30, 公開日: 2019-07-24, 最終更新日: 2023-10-11)

主引用文献

Teran, D.,Dolezelova, E.,Keough, D.T.,Hockova, D.,Zikova, A.,Guddat, L.W.
Crystal structures of Trypanosoma brucei hypoxanthine - guanine - xanthine phosphoribosyltransferase in complex with IMP, GMP and XMP.
Febs J., 286:4721-4736, 2019

PubMed Abstract: The 6-oxopurine phosphoribosyltransferases (PRTs) are drug targets for the treatment of parasitic diseases. This is due to the fact that parasites are auxotrophic for the 6-oxopurine bases relying on salvage enzymes for the synthesis of their 6-oxopurine nucleoside monophosphates. In Trypanosoma brucei, the parasite that is the aetiological agent for sleeping sickness, there are three 6-oxopurine PRT isoforms. Two are specific for hypoxanthine and guanine, whilst the third, characterized here, uses all three naturally occurring bases with similar efficiency. Here, we have determined crystal structures for TbrHGXPRT in complex with GMP, XMP and IMP to investigate the structural basis for substrate specificity. The results show that Y201 and E208, not commonly observed within the purine binding pocket of 6-oxopurine PRTs, contribute to the versatility of this enzyme. The structures further show that a nearby water can act as an adaptor to facilitate the binding of XMP and GMP. When GMP binds, a water can accept a proton from the 2-amino group but when XMP binds, the equivalent water can donate its proton to the 2-oxo group. However, when IMP is bound, no water molecule is observed at that location. DATABASE: Coordinates and structure factors were submitted to the Protein Data Bank and have accession codes of 6MXB, 6MXC, 6MXD and 6MXG for the TbrHGXPRT.XMP complex, TbrHGXPRT.GMP complex, TbrHGXPRT.IMP complex, and TbrHGPRT.XMP complex, respectively.

PubMed: 31287615
DOI: 10.1111/febs.14987

実験手法

X-RAY DIFFRACTION (1.993 Å)