Joint Center for Structural Genomics, La Jolla, California, United States of America.
PLoS One. 2011;6(7):e21875. doi: 10.1371/journal.pone.0021875. Epub 2011 Jul 25.
Imelysin-like proteins define a superfamily of bacterial proteins that are likely involved in iron uptake. Members of this superfamily were previously thought to be peptidases and were included in the MEROPS family M75. We determined the first crystal structures of two remotely related, imelysin-like proteins. The Psychrobacter arcticus structure was determined at 2.15 Å resolution and contains the canonical imelysin fold, while higher resolution structures from the gut bacteria Bacteroides ovatus, in two crystal forms (at 1.25 Å and 1.44 Å resolution), have a circularly permuted topology. Both structures are highly similar to each other despite low sequence similarity and circular permutation. The all-helical structure can be divided into two similar four-helix bundle domains. The overall structure and the GxHxxE motif region differ from known HxxE metallopeptidases, suggesting that imelysin-like proteins are not peptidases. A putative functional site is located at the domain interface. We have now organized the known homologous proteins into a superfamily, which can be separated into four families. These families share a similar functional site, but each has family-specific structural and sequence features. These results indicate that imelysin-like proteins have evolved from a common ancestor, and likely have a conserved function.
类糜蛋白酶蛋白家族定义了一个细菌蛋白超家族，这些蛋白可能参与铁的摄取。该超家族的成员以前被认为是肽酶，并被归入 MEROPS 家族 M75。我们测定了两个亲缘关系较远的类糜蛋白酶样蛋白的首个晶体结构。来自北极海生菌的结构在 2.15 Å 的分辨率下被确定，包含典型的糜蛋白酶折叠，而来自肠道细菌卵形拟杆菌的更高分辨率结构（在 1.25 Å 和 1.44 Å 的分辨率下）则具有环状移位拓扑结构。尽管序列相似性低且存在环状移位，这两种结构彼此之间仍高度相似。全螺旋结构可分为两个相似的四螺旋束结构域。整体结构和 GxHxxE 基序区域与已知的 HxxE 金属肽酶不同，表明类糜蛋白酶样蛋白不是肽酶。一个假定的功能位点位于结构域界面。我们现在将已知的同源蛋白组织成一个超家族，可以将其分为四个家族。这些家族共享一个相似的功能位点，但每个家族都具有特定的结构和序列特征。这些结果表明，类糜蛋白酶样蛋白是从一个共同的祖先进化而来的，并且可能具有保守的功能。
