Abstract：
Akkermansia muciniphila is a mucin-degrading probiotic that colonizes the gastrointestinal tract. Genomic analysis identified a set of genes involved in the biosynthesis of corrin ring, including the cobalt factor II methyltransferase CbiL, in some phylogroups of A. muciniphila, implying a potential capacity for de novo synthesis of cobalamin. In this work, we determined the crystal structure of CbiL from A. muciniphila at 2.3 Å resolution. AmCbiL exists as a dimer both in solution and in crystal, and each protomer consists of two α/β domains, the N-terminal domain and the C-terminal domain, consistent with the folding of typical class III MTases. The two domains create an open trough, potentially available to bind the substrates SAM and cobalt factor II. Sequence and structural comparisons with other CbiLs, assisted by computer modeling, suggest that AmCbiL should have cobalt factor II C-20 methyltransferase activity. Our results support that certain strains of A. muciniphila may be capable of synthesizing cobalamin de novo.
摘要：
Akkermansiamuciniphila是一种降解粘蛋白的益生菌，定植于胃肠道。基因组分析确定了一组参与corrin环生物合成的基因，包括钴因子II甲基转移酶CbiL，在A.muciniphila的一些系统组中，暗示从头合成钴胺素的潜在能力。在这项工作中,我们以2.3µ分辨率确定了A.muciniphila的CbiL的晶体结构。AmCbiL在溶液和晶体中均以二聚体形式存在,每个protomer由两个α/β结构域组成，N端域和C端域，与典型的III类MTases折叠一致。这两个区域形成了一个开放的槽，潜在地可用于结合底物SAM和钴因子II。与其他CBIL的序列和结构比较，在计算机建模的协助下，建议AmCbiL应具有钴因子IIC-20甲基转移酶活性。我们的结果支持某些粘蛋白A菌株可能能够从头合成钴胺素。
