Identity of a second type of allatostatin from cockroach brains: an octadecapeptide amide with a tyrosine-rich address sequence.
Identity of a second type of allatostatin from cockroach brains: an octadecapeptide amide with a tyrosine-rich address sequence.
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DOI：
10.1073/pnas.88.6.2412
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发表时间：
1991-03
影响因子：
11.1
通讯作者：
G. E. Pratt;D. Farnsworth;K. Fok;N. Siegel;A. McCormack;J. Shabanowitz;D. Hunt;R. Feyereisen
中科院分区：
文献类型：
--
作者：
G. E. Pratt;D. Farnsworth;K. Fok;N. Siegel;A. McCormack;J. Shabanowitz;D. Hunt;R. Feyereisen
通过高效液相色谱法从斑翅双翅蟑螂的脑-后脑复合体中分离出一种抑制保幼激素合成的十八肽。已通过串联质谱法阐明该Allatostatin的一级结构：Ala-Tyr-Ser-Tyr-Val-Ser-Glu-Tyr-Lys-Arg-Leu-Pro-Val-Tyr-Asn-Phe-Gly-Leu-NH 2（ASB 2）。这种B型allatostatin的酰胺化的三个残基C末端与四种已知的A型allatostatin的酰胺化的三个残基C末端相同，并且前面的三个残基显示出密切的结构同源性。ASB 2在抑制卵黄形成早期（第2天）雌性咽侧体中保幼激素生物合成方面的活性是A型十三肽Ala-Pro-Ser-Gly-Ala-Gln-Arg-Leu-Tyr-Gly-Phe-Gly-Leu-NH 2（ASA 1）的两倍以上，其效力在妊娠期间持续存在，但其对第10天雌性腺体的有效性与ASA 1相同（IC 50 = 0.31 nM）。十八肽的特征在于潜在的二元裂解位点，Lys 9-Arg 10，其完整性是高效力所需的。ASB 2-（11-18）-八肽酰胺在第10天在高浓度下产生完全应答（IC 50 = 48 nM），但ASB 2的C截短的（1-9）-、（1-11）-和（1-17）-酰胺片段无活性。因此，内分泌信息位于C末端。与非乙酰化肽相比，ASB 2的N-截短（9-18）、（10-18）和（11-18）片段的N α-乙酰化增加了活性。A型和B型allatostatin的作用位点位于保幼激素生物合成途径中甲羟戊酸激酶之前。
An octadecapeptide that inhibits juvenile hormone synthesis has been isolated by HPLC from brain-retrocerebral complexes of the cockroach Diploptera punctata. The primary structure of this allatostatin has been elucidated by tandem mass spectrometry: Ala-Tyr-Ser-Tyr-Val-Ser-Glu-Tyr-Lys-Arg-Leu-Pro-Val-Tyr-Asn-Phe-Gly-Leu- NH2 (ASB2). The amidated three-residue C terminus of this type B allatostatin is identical to that of four known type A allatostatins, and the preceding three residues show close structural homology. ASB2 has over twice the activity of the type A tridecapeptide Ala-Pro-Ser-Gly-Ala-Gln-Arg-Leu-Tyr-Gly-Phe-Gly-Leu-NH2 (ASA1) in inhibiting juvenile hormone biosynthesis in corpora allata from females in early vitellogenesis (day 2), and its efficacy persists during pregnancy, but it is equally effective as ASA1 on glands from day-10 females (IC50 = 0.31 nM). The octadecapeptide is characterized by a potential dibasic cleavage site, Lys9-Arg10, the integrity of which is needed for high potency. The ASB2-(11-18)-octapeptide amide gives a full response at high concentrations at day 10 (IC50 = 48 nM), but the C-truncated (1-9)-, (1-11)-, and (1-17)-amide fragments of ASB2 are inactive. Thus, the endocrine message is located at the C terminus. N alpha-acetylation of the N-truncated (9-18), (10-18), and (11-18) fragments of ASB2 increases activity relative to the nonacetylated peptides. The site of action of type A and type B allatostatins is located before mevalonate kinase in the biosynthetic pathway for juvenile hormone.