Molecular dynamics simulations of the periplasmic ferric-hydroxamate binding protein FhuD
Molecular dynamics simulations of the periplasmic ferric-hydroxamate binding protein FhuD
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DOI：
10.1007/s10534-005-3712-z
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发表时间：
2005-08-01
期刊：
影响因子：
3.5
通讯作者：
Vogel, HJ
中科院分区：
文献类型：
--
作者：
Krewulak, KD;Shepherd, CM;Vogel, HJ
FhuD是一种周质结合蛋白（PBP），在铁限制条件下，将各种异羟肟酸型铁载体从外膜受体（FhuA）转运到内膜ATP结合盒转运蛋白（FhuBC）。与许多其他PBPs不同，FhuD具有两个独立折叠的结构域，它们通过α-螺旋而不是两个或三个中心β-链连接。具有和不具有结合的没食子色素的FhuD的晶体结构提供了对铁载体结合机制的一些见解，并且提出了FhuD与FhuB结合的潜在机制。由于连接两个结构域的α-螺旋相对于其他“经典”PBPs中的β-链对结构施加了更大的刚性，因此这些结构在结合异羟肟酸盐型铁载体时没有显示出大的构象变化。因此，很难解释内膜转运蛋白FhuB如何区分铁色素结合和无铁色素的FhuD。在目前的研究中，我们采用了30 ns的分子动力学模拟FhuD与其结合的铁载体删除，以探讨FhuD在无底物状态下的动力学行为。MD模拟表明，FhuD在释放其铁载体时具有6度的C-末端结构域闭合，在某种程度上是动态的。这种相对较大的运动表明，FhuB可以区分铁色素结合和无铁色素的FhuD。
FhuD is a periplasmic binding protein (PBP) that, under iron-limiting conditions, transports various hydroxamate-type siderophores from the outer membrane receptor (FhuA) to the inner membrane ATP-binding cassette transporter (FhuBC). Unlike many other PBPs, FhuD possesses two independently folded domains that are connected by an alpha-helix rather than two or three central beta-strands. Crystal structures of FhuD with and without bound gallichrome have provided some insight into the mechanism of siderophore binding as well as suggested a potential mechanism for FhuD binding to FhuB. Since the alpha-helix connecting the two domains imposes greater rigidity on the structure relative to the beta-strands in other 'classical' PBPs, these structures reveal no large conformational change upon binding a hydroxamate-type siderophore. Therefore, it is difficult to explain how the inner membrane transporter FhuB can distinguish between ferrichrome-bound and ferrichrome-free FhuD. In the current study, we have employed a 30 ns molecular dynamics simulation of FhuD with its bound siderophore removed to explore the dynamic behavior of FhuD in the substrate-free state. The MD simulation suggests that FhuD is somewhat dynamic with a C-terminal domain closure of 6 degrees upon release of its siderophore. This relatively large motion suggests differences that would allow FhuB to distinguish between ferrichrome-bound and ferrichrome-free FhuD.