ATP-BINDING SITE OF ADENYLATE KINASE - MECHANISTIC IMPLICATIONS OF ITS HOMOLOGY WITH RAS-ENCODED P21, F1-ATPASE, AND OTHER NUCLEOTIDE-BINDING PROTEINS
ATP-BINDING SITE OF ADENYLATE KINASE - MECHANISTIC IMPLICATIONS OF ITS HOMOLOGY WITH RAS-ENCODED P21, F1-ATPASE, AND OTHER NUCLEOTIDE-BINDING PROTEINS
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DOI：
10.1073/pnas.83.4.907
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发表时间：
1986-02-01
影响因子：
11.1
通讯作者：
MILDVAN, AS
中科院分区：
文献类型：
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作者：
FRY, DC;KUBY, SA;MILDVAN, AS
通过核磁共振和x射线衍射的结合，发现腺苷酸激酶的MgATP结合位点位于3个蛋白质片段附近，长度为5 - 7个氨基酸，与其他核苷酸结合的磷酸转移酶（如肌球蛋白和f1 - atp酶、ras p21和转导蛋白gtp酶、camp依赖蛋白激酶和src蛋白激酶）中的片段序列同源，表明这些片段在所有这些蛋白中都具有相同的机制作用。片段1是一个富含甘氨酸的柔性环，在腺苷酸激酶上，可以通过改变其构象来控制进入atp结合位点。第2段是一个含有两个疏水残基的α -螺旋，它们与ATP的腺嘌呤核糖部分相互作用，还有一个赖氨酸可以与ATP的-磷酸和-磷酸结合。第3节段是一条疏水链，由一个羧酸盐终止，位于三磷酸结合位点的两侧。已报道的ras p21转化为转化剂的各种突变似乎都涉及第1片段，这种取代可能通过阻碍该片段的构象变化来改变p21的性质。在f1 -ATP酶中，柔性环可以通过其位置控制酶的可及性和ATP/ADP平衡常数。
The MgATP binding site of adenylate kinase, located by a combination of NMR and x-ray diffraction, is near three protein segments, five to seven amino acids in length, that are homologous in sequence to segments found in other nucleotide-binding phosphotransferases, such as myosin and F1-ATPase, ras p21 and transducin GTPases, and cAMP-dependent and src protein kinases, suggesting equivalent mechanistic roles of these segments in all of these proteins. Segment 1 is a glycine-rich flexible loop that, on adenylate kinase, may control access to the ATP-binding site by changing its conformation. Segment 2 is an alpha-helix containing two hydrophobic residues that interact with the adenine-ribose moiety of ATP, and a lysine that may bind to the beta- and gamma-phosphates of ATP. Segment 3 is a hydrophobic strand of parallel beta-pleated sheet, terminated by a carboxylate, that flanks the triphosphate binding site. The various reported mutations of ras p21 that convert it to a transforming agent all appear to involve segment 1, and such substitutions may alter the properties of p21 by hindering a conformational change at this segment. In F1-ATPase, the flexible loop may, by its position, control both the accessibility and the ATP/ADP equilibrium constant on the enzyme.