首页 | 本学科首页   官方微博 | 高级检索  
     


Structural insights into selectivity and cofactor binding in snake venom L-amino acid oxidases
Authors:Ullah A  Souza T A C B  Abrego J R B  Betzel C  Murakami M T  Arni R K
Affiliation:1. Centro Multiusuário de Inovação Biomolecular, Departamento de Física, Universidade Estadual Paulista (UNESP), 15054-000 São José do Rio Preto, SP, Brazil;2. Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, 13083-970 SP, Brazil;3. Institute of Biochemistry and Molecular Biology, University of Hamburg, Laboratory of Structural Biology of Infection and Inflammation, c/o DESY, Notkestrasse 85, Build. 22a, D-22603 Hamburg, Germany
Abstract:l-Amino acid oxidases (LAAOs) are flavoenzymes that catalytically deaminate l-amino acids to corresponding α-keto acids with the concomitant production of ammonia (NH3) and hydrogen peroxide (H2O2). Particularly, snake venom LAAOs have been attracted much attention due to their diverse clinical and biological effects, interfering on human coagulation factors and being cytotoxic against some pathogenic bacteria and Leishmania ssp. In this work, a new LAAO from Bothrops jararacussu venom (BjsuLAAO) was purified, functionally characterized and its structure determined by X-ray crystallography at 3.1 Å resolution. BjsuLAAO showed high catalytic specificity for aromatic and aliphatic large side-chain amino acids. Comparative structural analysis with prokaryotic LAAOs, which exhibit low specificity, indicates the importance of the active-site volume in modulating enzyme selectivity. Surprisingly, the flavin adenine dinucleotide (FAD) cofactor was found in a different orientation canonically described for both prokaryotic and eukaryotic LAAOs. In this new conformational state, the adenosyl group is flipped towards the 62–71 loop, being stabilized by several hydrogen-bond interactions, which is equally stable to the classical binding mode.
Keywords:
本文献已被 ScienceDirect PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号