Nnal‐like proteins are active metallocarboxypeptidases of a new and diverse M14 subfamily
Nnal‐like proteins are active metallocarboxypeptidases of a new and diverse M14 subfamily
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Nnal 样蛋白是一种新的、多样化的 M14 亚家族的活性金属羧肽酶
DOI：
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
F. Avilés
中科院分区：
文献类型：
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作者：
M. Vega;R. G. Sevilla;A. Hermoso;J. Lorenzo;S. Tanco;A. Diez;L. Fricker;J. Bautista;F. Avilés
Nnal与金属羧肽酶具有一定的序列相似性，但其生化特性尚未见报道。在这项工作中，我们进行了详细的基因组扫描，并在细菌、原生生物和动物中发现了100个nal同源物，包括大多数真核生物物种中的几个相似物。Nnal - like序列的系统发育分析表明，Nnal - like肽酶与先前已知的金属羧基肽酶亚家族（M14A、M14B和M14C）之间存在主要差异。对来自多种物种的具有代表性的Nnal样蛋白的构象建模表明，Nnal样蛋白具有异常开放的活性位点，这一特性可能有助于其在多种肽和蛋白质底物上发挥作用。为了验证这一点，我们表达了一种来自caenσ横纹肌线虫的Nnal样肽酶的重组形式，并证明该蛋白是一种功能齐全的metaucarboxypeptidase，可以从合成肽中切割一系列C末端氨基酸。酶活性被ATP/ADP激活和盐失活，并优先被Z‐Glu‐Tyr二肽抑制，这在金属羧肽酶中是没有先例的，类似于微管蛋白羧肽酶的功能；这一假设被Kalinina等人在该期刊上发表的论文(1)中所描述的结果强有力地加强了。我们的研究结果表明，金属羧基肽酶M14家族比预期的更复杂和多样化，Nnal样肽酶是这些酶的功能变体，代表了一个新的亚家族（我们建议命名为M14D），它对这种多样性有很大贡献。-Rodriguez de la Vega， M., Sevilla， R. G., Hermoso， A., Lorenzo， J., Tanco， S., Diez， A., Fricker， L. D., Bautista， J. M., avilsams， F. X. Nna1 - like蛋白是一种新的和多样化的M14亚家族的活性金属羧肽酶。中华医学杂志，20,851-865 （2007）
Nnal has some sequence similarity to metallocarboxypeptidases, but the biochemical characterization of Nnal has not previously been reported. In this work we performed a detailed genomic scan and found >100 Nnal homologues in bacteria, Protista, and Anima‐lia, including several paralogs in most eukaryotic species. Phylogenetic analysis of the Nnal‐like sequences demonstrates a major divergence between Nnal‐like peptidases and the previously known metallocarboxypeptidases subfamilies: M14A, M14B, and M14C. Conformational mod‐eling of representative Nnal‐like proteins from a variety of species indicates an unusually open active site, a property that might facilitate its action on a wide variety of peptide and protein substrates. To test this, we expressed a recombinant form of one of the Nnal‐like peptidases from Caenσrhabditis elegans and demonstrated that this protein is a fully functional metaUocarboxypeptidase that cleaves a range of C‐terminal amino acids from synthetic peptides. The enzymatic activity is activated by ATP/ADP and salt‐inactivated, and is preferentially inhibited by Z‐Glu‐Tyr dipeptide, which is without precedent in metallocarboxypeptidases and resembles tubulin carboxypeptidase functioning; this hypothesis is strongly reinforced by the results depicted in Kalinina et al. published as accompanying paper in this journal (1). Our findings demonstrate that the M14 family of metallocarboxypeptidases is more complex and diverse than expected, and that Nnal‐like peptidases are functional variants of such enzymes, representing a novel subfamily (we propose the name M14D) that contributes substantially to such diversity.—Rodriguez de la Vega, M., Sevilla, R. G., Hermoso, A., Lorenzo, J., Tanco, S., Diez, A., Fricker, L. D., Bautista, J. M., Avilés, F. X. Nna1‐like proteins are active metallocarboxypeptidases of a new and diverse M14 subfamily. FASEB J. 20, 851–865 (2007)
神经和肌肉分化过程中细胞质微管蛋白羧肽酶活性的调节：使用基于微管的测定进行表征。
影响因子：
2.9
作者：
Webster,DR;Modesti,NM;Bulinski,JC
通讯作者：
Bulinski,JC
DOI：
10.1073/pnas.83.20.7568
发表时间：
1986-10-01
影响因子：
11.1
作者：
CHRISTIANSON, DW;LIPSCOMB, WN
通讯作者：
LIPSCOMB, WN