Structure of a premicellar complex of alkyl sulfates with the interfacial binding surfaces of four subunits of phospholipase A2.

Structure of a premicellar complex of alkyl sulfates with the interfacial binding surfaces of four subunits of phospholipase A2.
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DOI:
10.1016/j.bbapap.2010.03.004
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发表时间:
2010-07
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Bahnson BJ
Bahnson BJ
中科院分区:
其他
文献类型:
--
作者:
Pan YH;Bahnson BJ

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猪胰腺IB族分泌的磷脂酶A2(sPLA 2)与单分散烷基硫酸盐的三种离散的预胶束复合物(E1#、E2#、E3 #)的性质已经被表征[贝格,O. G.,例如,Biochemistry 43,7999-8013,2004]。在这里,我们已经解决了与12个硫酸辛酯(C8 S)分子复合的IB组sPLA 2的2.7 μ m晶体结构,其形式与存在于预胶束复合物的E1#相期间的四聚体低聚物一致。C8 S分子的烷基尾集中在sPLA 2亚基的四聚体簇的中间。四个sPLA 2亚基中的三个也在活性位点口袋中含有C8 S分子。C8 S配体的硫酸根氧与4个蛋白质活性位点中的3个中的活性位点钙络合。烷基硫酸盐头基与Arg-6和Lys-10以及Met-20的骨架酰胺的相互作用类似于先前解析的具有结合的磷酸盐和硫酸盐阴离子的sPLA 2晶体结构中观察到的那些。在本结构中发现的三个阴离子的簇被假定为成核的阴离子两亲物的蛋白质的界面表面的结合的网站,因此,这种结合相互作用的酶的界面激活的影响。
The properties of three discrete premicellar complexes (E1#, E2#, E3#) of pig pancreatic group-IB secreted phospholipase A2 (sPLA2) with monodisperse alkyl sulfates has been characterized [Berg, O. G., et al., Biochemistry 43, 7999–8013, 2004]. Here we have solved the 2.7 Å crystal structure of group-IB sPLA2 complexed with 12 molecules of octyl sulfate (C8S) in a form consistent with a tetrameric oligomeric that exists during the E1# phase of premicellar complexes. The alkyl tails of the C8S molecules are centered in the middle of the tetrameric cluster of sPLA2 subunits. Three of the four sPLA2 subunits also contain a C8S molecule in the active site pocket. The sulfate oxygen of a C8S ligand is complexed to the active site calcium in 3 of the 4 protein active sites. The interactions of the alkyl sulfate head group with Arg-6 and Lys-10, as well as the backbone amide of Met-20, are analogous to those observed in the previously solved sPLA2 crystal structures with bound phosphate and sulfate anions. The cluster of three anions found in the present structure is postulated to be the site for nucleating the binding of anionic amphiphiles to the interfacial surface of the protein, and therefore this binding interaction has implications for interfacial activation of the enzyme.
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影响因子: 2.9
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期刊: ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子: --
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影响因子: --
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