Structural changes common to catalysis in the Tpx peroxiredoxin subfamily.
Structural changes common to catalysis in the Tpx peroxiredoxin subfamily.
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DOI：
10.1016/j.jmb.2009.08.040
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发表时间：
2009-11-06
影响因子：
5.6
通讯作者：
Karplus, P. Andrew
中科院分区：
文献类型：
--
作者：
Hall, Andrea;Sankaran, Banumathi;Poole, Leslie B.;Karplus, P. Andrew
硫醇过氧化物酶（Tpxs）是来自细菌的二聚体2-胱氨酸过氧化物酶，它优先还原烷基过氧化物。催化需要两个保守残基，即过氧化物半胱氨酸和分解半胱氨酸，它们分别位于螺旋α2和螺旋α3上。在催化过程中，α2和α3螺旋的部分解开允许在这两个残基之间形成分子内二硫化物。在这里，我们展示了大肠杆菌Tpx的三种结构，分别代表完全折叠（FF，过氧化物结合位点完整），局部展开（LU，二硫键）和部分局部展开（PLU，过渡态）的构象。我们还比较了已知的Tpx晶体结构，并分析了近300个Tpx序列的序列保守模式。12个完全保守的tpx特异性残基聚集在活性位点和二聚体界面上，另外37个高度保守的残基大多位于为螺旋α2提供环境的摇篮中。使用这里确定的结构作为代表性的FF，过渡和LU Tpx构象，我们详细描述了与Tpx亚族催化相关的结构变化。关键的见解包括在活性位点周围的保守疏水环的描述，α2和α3螺旋之间的一组保守的包装相互作用，允许α2的局部展开触发α3的部分展开，一个保守的二聚体界面，锚定α2和α3螺旋的末端，在结构转变期间稳定活性位点。一组保守的残基构成了一个摇篮，稳定了参与催化的螺旋α2的两个离散构象。二聚体界面参与稳定活性位点折叠和形成疏水环，这表明Tpx是专性二聚体，并解释了界面残基的高度守恒。
Thiol peroxidases (Tpxs) are dimeric 2-Cys peroxiredoxins from bacteria that preferentially reduce alkyl hydroperoxides. Catalysis requires two conserved residues, the peroxidatic cysteine and the resolving cysteine, which are located in helix α2 and helix α3, respectively. The partial unraveling of helices α2 and α3 during catalysis allows for the formation of an intramolecular disulfide between these two residues. Here we present three structures of Escherichia coli Tpx representing the fully folded (FF, peroxide binding site intact), locally unfolded (LU, disulfide bond), and partially locally unfolded (PLU, transitional state) conformations. We also compare known Tpx crystal structures and analyze the sequence-conservation patterns among nearly 300 Tpx sequences. Twelve fully conserved Tpx-specific residues cluster at the active site and dimer interface, and an additional 37 highly conserved residues are mostly located in a cradle providing the environment for helix α2. Using the structures determined here as representative FF, transitional, and LU Tpx conformations, we describe in detail the structural changes associated with catalysis in the Tpx subfamily. Key insights include the description of a conserved hydrophobic collar around the active site, a set of conserved packing interactions between helices α2 and α3 that allow the local unfolding of α2 to trigger the partial unfolding of α3, a conserved dimer interface that anchors the ends of helices α2 and α3 to stabilize the active site during structural transitions, and a conserved set of residues constituting a cradle that stabilizes the two discrete conformations of helix α2 involved in catalysis. The involvement of the dimer interface in stabilizing active-site folding and in forming the hydrophobic collar implies that Tpx is an obligate homodimer and explains the high conservation of interface residues.
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DOI：
10.1107/s0907444999016261
发表时间：
2000-03-01
影响因子：
2.2
作者：
Burmeister, WP
通讯作者：
Burmeister, WP
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
14.9
作者：
Landau M;Mayrose I;Rosenberg Y;Glaser F;Martz E;Pupko T;Ben-Tal N
通讯作者：
Ben-Tal N
影响因子：
4.8
作者：
CHA, MK;KIM, HK;KIM, IH
通讯作者：
KIM, IH