Developing an energy landscape for the novel function of a (β/α)8 barrel:: Ammonia conduction through HisF
Developing an energy landscape for the novel function of a (β/α)8 barrel:: Ammonia conduction through HisF
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DOI：
10.1073/pnas.1331150100
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发表时间：
2003-06-24
影响因子：
11.1
通讯作者：
Luthey-Schulten, Z
中科院分区：
文献类型：
--
作者：
Amaro, R;Tajkhorshid, E;Luthey-Schulten, Z
HISF是一个多结构域的球状蛋白复合体；HISF是一种I类谷氨酰胺氨基转移酶，它能将谷氨酰胺分解成氨；HISF是一种(β/α)(8)桶状环化酶，完成咪唑甘油磷酸合成酶的环化。HISH和HISF共同形成谷氨酰胺氨基转移酶，执行组氨酸生物合成途径的第五步。最近，有人提出(β/α)(8)桶参与了一种新的功能：将氨从HISH的活性部位引导到HISF的活性部位。本研究提供了一系列分子动力学模拟来研究HISF的沟道函数。本文重建了氨在通道中传导的平均力势，以及氨通过严格守恒的通道门的入口，在封闭和假想的开放构象下。通道内由此产生的能量格局支持这样的观点，即氨确实通过了管子，在此过程中与保守的亲水性残基相互作用。所提出的开放构象，包括一个门残基的交替旋转态，对氨进入只提供了大约2.5千卡的能量势垒。通过生物信息学推导出另一种可能在非固氮生物体中发挥作用的替代开放门构象。
HisH-hisF is a multidomain globular protein complex; hisH is a class I glutamine amidotransferase that hydrolyzes glutamine to form ammonia, and hisF is a (beta/alpha)(8) barrel cyclase that completes the ring formation of imidizole glycerol phosphate synthase. Together, hisH and hisF form a glutamine amidotransferase that carries out the fifth step of the histidine biosynthetic pathway. Recently, it has been suggested that the (beta/alpha)(8) barrel participates in a novel function: to channel ammonia from the active site of hisH to the active site of hisF. The present study presents a series of molecular dynamic simulations that investigate the channeling function of hisF. This article reconstructs potentials of mean force for the conduction of ammonia through the channel, and the entrance of ammonia through the strictly conserved channel gate, in both a closed and a hypothetical open conformation. The resulting energy landscape within the channel supports the idea that ammonia does indeed pass through the barrel, interacting with conserved hydrophilic residues along the way. The proposed open conformation, which involves an alternate rotamer state of one of the gate residues, presents only an approximate to2.5-kcal energy barrier to ammonia entry. Another alternate open-gate conformation, which may play a role in non-nitrogen-fixing organisms, is deduced through bioinformatics.