Docking and small angle X-ray scattering studies of purine nucleoside phosphorylase

被引：43

作者：

de Azevedo, WF ^{[1
]}

dos Santos, GC

dos Santos, DM

Olivieri, JR

Canduri, F

Silva, RG

Basso, LA

Renard, G

da Fonseca, IO

Mendes, MA

Palma, MS

Santos, DS

机构：

[1] UNESP, Dept Fis, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil

[2] Inst Butantan, Ctr Appl Toxinol, BR-05503900 Sao Paulo, Brazil

[3] Univ Fed Rio Grande do Sul, Dept Biol Mol & Biotecnol, Rede Brasileira Pesquisas TB, BR-91501970 Porto Alegre, RS, Brazil

[4] UNESP, Inst Biosci, Dept Biol, Lab Struct Biol & Zoochem, BR-13506900 Rio Claro, SP, Brazil

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 309卷 / 04期

基金：

巴西圣保罗研究基金会;

关键词：

geometric docking; SAXS; purine nucleoside phosphorylase; bioinformatics;

D O I：

10.1016/j.bbrc.2003.08.093

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Docking simulations have been used to assess protein complexes with some success. Small angle X-ray scattering (SAXS) is a well-established technique to investigate protein spatial configuration. This work describes the integration of geometric docking with SAXS to investigate the quaternary structure of recombinant human purine nucleoside phosphorylase (PNP). This enzyme catalyzes the reversible phosphorolysis of N-ribosidic bonds of purine nucleosides and deoxynucleosides. A genetic deficiency due to mutations in the gene encoding for PNP causes gradual decrease in T-cell immunity. Inappropriate activation of T-cells has been implicated in several clinically relevant human conditions such as transplant rejection, rheumatoid arthritis, lupus, and T-cell lymphomas. PNP is therefore a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. The present analysis confirms the trimeric structure observed in the crystal. The potential application of the present procedure to other systems is discussed. (C) 2003 Elsevier Inc. All rights reserved.

引用

页码：923 / 928

页数：6

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