Accommodating a nonconservative internal mutation by water-mediated hydrogen bonding between β-sheet strands: a comparison of human and rat type B (mitochondrial) cytochrome b5.
Accommodating a nonconservative internal mutation by water-mediated hydrogen bonding between β-sheet strands: a comparison of human and rat type B (mitochondrial) cytochrome b5.
复制标题
DOI：
10.1021/bi2004729
复制
发表时间：
2011-06-21
期刊：
影响因子：
2.9
通讯作者：
Benson DR
中科院分区：
文献类型：
--
作者：
Parthasarathy S;Altuve A;Terzyan S;Zhang X;Kuczera K;Rivera M;Benson DR
哺乳动物B型（线粒体）细胞色素b5比它们的A型（微粒体）对应物表现出更大的氨基酸序列多样性，如来自人（hCYB 5 B）和大鼠（rCYB 5 B）的B型蛋白质所例示。本文报道的hCYB5B和rCYB5B的X射线晶体结构的比较揭示了涉及五链β折叠的包装的显著差异，这可归因于链β4中完全掩埋的残基21。与rCYB5B中的Thr21相比，hCYB5B中的Leu21的体积更大，导致β5中的前两个残基的大量置换，以及β5和β4之间的三个氢键中的两个的损失。残基之间的氢键是由两个有序的、完全掩埋的水分子介导的。在10 ns的分子动力学模拟中，hCYB5B结构中的一个埋藏水分子通过具有夹在β4和β5之间的三个水分子的中间体容易地与溶剂交换。当在第二次10 ns模拟之前去除掩埋的水分子时，β4和β5形成与rCYB5B中相同的持久氢键，但Leu21侧链被迫采用很少观察到的构象。尽管这些观察结果表明hCYB5B比rCYB5B更容易进入内部，但这两种蛋白质表现出几乎相同的稳定性，动态和氧化还原性质。这些结果为细胞色素b5折叠的稳定因素提供了新的见解。
Mammalian type B (mitochondrial) cytochromes b5 exhibit greater amino acid sequence diversity than their type A (microsomal) counterparts, as exemplified by the type B proteins from human (hCYB5B) and rat (rCYB5B). The comparison of X-ray crystal structures of hCYB5B and rCYB5B reported herein reveals a striking difference in packing involving the five-stranded β-sheet, attributable to fully buried residue 21 in strand β4. The greater bulk of Leu21 in hCYB5B in comparison to Thr21 in rCYB5B results in a substantial displacement of the first two residues in β5, and consequent loss of two of the three hydrogen bonds between β5 and β4. Hydrogen-bonding between the residues is instead mediated by two well-ordered, fully buried water molecules. In a 10 ns molecular dynamics simulation, one of the buried water molecules in the hCYB5B structure exchanged readily with solvent via intermediates having three water molecules sandwiched between β4 and β5. When the buried water molecules were removed prior to a second 10 ns simulation, β4 and β5 formed persistent hydrogen bonds identical to those in rCYB5B, but the Leu21 side chain was forced to adopt a rarely observed conformation. Despite the apparently greater ease of water access to the interior of hCYB5B than of rCYB5B suggested by these observations, the two proteins exhibit virtually identical stability, dynamic and redox properties. The results provide new insight into the factors stabilizing the cytochrome b5 fold.
登录
查看更多内容
影响因子：
4.5
作者：
ARMSTRONG, FA;COX, PA;OLIVER, BN
通讯作者：
OLIVER, BN
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
DOI：
10.1002/prot.340040208
发表时间：
1988-01-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
BRUNGER, AT;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
2.9
作者：
Cowley, AB;Sun, N;Benson, DR
通讯作者：
Benson, DR
影响因子：
2.9
作者：
Cowley, AB;Altuve, A;Benson, DR
通讯作者：
Benson, DR