Dipeptidyl-peptidases: Key enzymes producing entry forms of extracellular proteins in asaccharolytic periodontopathic bacterium Porphyromonas gingivalis.

Dipeptidyl-peptidases: Key enzymes producing entry forms of extracellular proteins in asaccharolytic periodontopathic bacterium Porphyromonas gingivalis.
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DOI:
10.1111/omi.12317
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发表时间:
2021-04
影响因子:
3.7
通讯作者:
Ohara Nemoto Y
Ohara Nemoto Y
中科院分区:
医学3区
文献类型:
--
作者:
Nemoto TK;Ohara Nemoto Y

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牙龈卟啉单胞菌(Porphyromonas gingivalis)是一种能分解唾液酸的微生物,它只利用营养性氨基酸作为能量来源和细胞成分。细菌被认为主要以二肽的形式掺入蛋白质营养物,因此从多肽产生二肽的外肽酶对于存活和增殖至关重要。我们在此概述了由二肽基肽酶(DPP)介导的牙龈卟啉单胞菌的二肽生产,例如,DPP 4、DPP 5、DPP 7和DPP 11是位于周质中的丝氨酸外肽酶,其从多肽的N末端释放二肽。此外,另外两种外肽酶,酰基肽基寡肽酶(AOP)和脯氨酰三肽基肽酶A(PTP-A),其分别释放N-末端酰化的二肽/三肽和三肽,其中Pro在第三位置,提供DPP可接受形式的多肽。因此,大部分二肽是由具有不同特异性的DPP与AOP和PTP-A组合从营养多肽产生的。然后,所得的二肽主要通过质子依赖性寡肽转运蛋白(POT)(主要易化剂超家族的成员)跨内膜掺入。最近的研究还表明,DPP 4和DPP 7分别与牙周和全身性疾病(如2型糖尿病和凝血异常)直接相关。因此,这些二肽产生和掺入分子被认为是预防和治疗牙周病和相关全身性疾病的有效靶点。
Porphyromonas gingivalis, a pathogen of chronic periodontitis, is an asaccharolytic microorganism that solely utilizes nutritional amino acids as its energy source and cellular constituents. The bacterium is considered to incorporate proteinaceous nutrients mainly as dipeptides, thus exopeptidases that produce dipeptides from polypeptides are critical for survival and proliferation. We present here an overview of dipeptide production by P. gingivalis mediated by dipeptidyl‐peptidases (DPPs), e.g., DPP4, DPP5, DPP7, and DPP11, serine exopeptidases localized in periplasm, which release dipeptides from the N‐terminus of polypeptides. Additionally, two other exopeptidases, acylpeptidyl‐oligopeptidase (AOP) and prolyl tripeptidyl‐peptidase A (PTP‐A), which liberate N‐terminal acylated di‐/tri‐peptides and tripeptides with Pro at the third position, respectively, provide polypeptides in an acceptable form for DPPs. Hence, a large fraction of dipeptides is produced from nutritional polypeptides by DPPs with differential specificities in combination with AOP and PTP‐A. The resultant dipeptides are then incorporated across the inner membrane mainly via a proton‐dependent oligopeptide transporter (POT), a member of the major facilitator superfamily. Recent studies also indicate that DPP4 and DPP7 directly link between periodontal and systemic diseases, such as type 2 diabetes mellitus and coagulation abnormality, respectively. Therefore, these dipeptide‐producing and incorporation molecules are considered to be potent targets for prevention and treatment of periodontal and related systemic diseases.
DOI: 10.1371/journal.pone.0043019
发表时间: 2012-08-29
期刊: PLOS ONE
影响因子: 3.7
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发表时间: 2017-03-01
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