Molecular Biology Lab, Regional Research Institute of Unani Medicine, Hazrat Bal, Kashmir University Campus, Srinagar, Jammu & Kashmir, India.
Gene. 2013 Mar 10;516(2):316-9. doi: 10.1016/j.gene.2012.12.070. Epub 2012 Dec 31.
Prolidase deficiency (PD) is a rare inborn disorder of collagen metabolism characterized by chronic recurrent cutaneous ulceration. We report a novel 3 bp insertion in the 12th exon of the PEPD gene in two Kashmiri siblings with prolidase deficiency phenotype. This mutation results in addition of an extra alanine residue at the amino-acid position number 304 of prolidase peptide. The structural analysis showed that this Ala insertion is located at the helix (a.a. 300-320), which contains several important hydrogen bonds between residues essential for structural folding for the enzyme activity. In silico analysis suggests that this insertion mutation might distort or bend the helical feature to affect the hydrogen-bond network between residues of neighboring secondary structures and deform the metal-binding geometry of the enzyme. Although approximately 70 PEPD gene mutations and polymorphisms have been reported in various ethnic groups, we however report, for the first time, the identification of insertion mutation in human the PEPD gene.
脯肽酶缺乏症（PD）是一种罕见的先天性胶原代谢紊乱，其特征为慢性复发性皮肤溃疡。我们报道了一对患有脯肽酶缺乏表型的克什米尔兄弟中 12 号外显子的 3bp 插入突变。该突变导致脯肽酶肽第 304 位氨基酸额外增加一个丙氨酸残基。结构分析表明，该 Ala 插入位于螺旋（a.a. 300-320），其中包含几个重要的氢键，这些氢键对于酶活性的结构折叠至关重要。计算机分析表明，这种插入突变可能会扭曲或弯曲螺旋特征，影响相邻二级结构之间的残基氢键网络，并改变酶的金属结合几何形状。尽管已经在不同种族中报道了大约 70 种 PEPD 基因突变和多态性，但我们首次在人类的 PEPD 基因中发现了插入突变。
