三维结构的adenosylcobinamide磷酸激酶/ adenosylcobinamide guanylyltransferase (CobU)与GMP:证据substrate-induced转移酶活性部位。

文章的细节

引用

汤普森结核病,托马斯毫克,Escalante-Semerena JC, Rayment我

三维结构的adenosylcobinamide磷酸激酶/ adenosylcobinamide guanylyltransferase (CobU)与GMP:证据substrate-induced转移酶活性部位。

生物化学。1999年10月5日,38 (40):12995 - 3005。

PubMed ID
10529169 (在PubMed
]
文摘

adenosylcobinamide x射线晶体结构的磷酸激酶/ adenosylcobinamide guanylyltransferase (CobU)鼠伤寒沙门氏菌绑定到GMP一直由分子置换2.2决议。CobU是一种双功能酶,它催化的磷酸化1-amino-O-2-propanol adenosylcobinamide环侧链和随后的功能作为guanylyltransferase adenosylcobinamide.GDP形式。转移酶活动包括共价enzyme-guanylyl中间,最有可能phosphoramidate联系他(46)。之前的研究表明,这种酶是homotrimer采用一个纸风车形状。每个单元由六个平行beta-strands和单个域的一个反平行的链在两侧,共有五个阿尔法螺旋和一个螺旋。有趣的是,他在酶蛋白(46)位于相当距离激酶活性部位或P-loop图案和solvent-exposed(汤普森,t . B。et al。(1998)生物化学37岁,7686 - 7695]。检查两个活动网站的结构关系,CobU共晶三磷酸鸟苷和焦磷酸。水晶属于空间群P2(1) 2(1) 2(1)与以下单位细胞维度:a = 58岁。4 A、b = 87.8 A和c = 101.6。结构显示了水解产物GMP电子密度,而不是预期的共价guanylyl中间似乎是水解的晶格。 Even so, CobU exhibits a substantial conformational rearrangement. The helix axis containing His(46), the site of guanylylation, rotates 30 degrees and translates 11 A relative to the apo structure and is accompanied by compensatory unwinding and rewinding at the helix ends to allow the induction of a guanosine binding pocket between beta-strand 2 and alpha-helix 2. This conformational change brings the C(alpha) of His(46) approximately 10 A closer to the P-loop motif such that a phosphate ion located in the P-loop is only 6 A from the alpha-phosphate of GMP. This suggests that the P-loop motif may be used to coordinate the terminal phosphates in both the transferase and kinase reactions and implies that the active sites for both reactions overlap.

DrugBank数据引用了这篇文章

多肽
的名字 UniProt ID
双官能adenosylcobalamin CobU生物合成蛋白质 Q05599 细节