Structural insights into the activation mechanisms of human HtrA serine proteases

Żurawa-Janicka, Dorota; Wenta, Tomasz; Jarzab, Miroslaw; Skórko-Glonek, Joanna; Glaza, Przemysław; Giełdoń, Artur; Ciarkowski, Jerzy; Lipińska, Barbara

doi:10.1016/j.abb.2017.04.004

Cited by 66 publications

(85 citation statements)

References 141 publications

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“…Further analysis of prokaryotic and viral proteases also show that all proteases of set II have the catalytically competent or incompetent conformation of catalytic histidine, but all proteases of set III have only the catalytically competent conformation of the catalytic histidine (Table S1, column 4). The structural diversity of the side chain of Asn55 T agrees well with the conformational changes in the active sites of the HtrA family proteases [25][26][27]29].…”

Section: Nucleophile-base Catalytic Zone (Nbczone) Of Trypsinsupporting

confidence: 57%

“…In contrast, with the bovine protein C as an example, replacing this alanine with a hydrophobic valine does not cause major changes in the conformation of the catalytic histidine [17]. Tables 1 and S1), joined together into HtrA family [25,26]. In these enzymes the 54 T position is occupied by only threonine, and thus, this group of HtrA family proteases was named the "TN group".…”

Section: Nucleophile-base Catalytic Zone (Nbczone) Of Trypsinmentioning

confidence: 99%

“…The HtrA family proteases are multidomain proteins, which besides a proteolytic domain also contain at least one C-terminal PDZ domain [25,26]. The functional unit of the HtrA family proteases ranges from a trimer to a dodecamer.…”

Section: Nucleophile-base Catalytic Zone (Nbczone) Of Trypsinmentioning

confidence: 99%

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NBCZone: Universal three-dimensional construction of eleven amino acids near the catalytic nucleophile and base in the superfamily of (chymo)trypsin-like serine fold proteases

Denesyuk

Johnson

Salo‐Ahen

et al. 2020

International Journal of Biological Macromolecules

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publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Journal Pre-proof NBCZone: Universal three-dimensional construction of eleven amino acids near the catalytic nucleophile and base in the superfamily of (chymo)trypsin-like serine fold proteases Please cite this article as: A.I. Denesyuk, M.S. Johnson, O.M.H. Salo-Ahen, et al., NBCZone: Universal three-dimensional construction of eleven amino acids near the catalytic nucleophile and base in the superfamily of (chymo)trypsin-like serine fold proteases, International Journal of Biological Macromolecules(2020), https://doi.Journal Pre-proof J o u r n a l P r e -p r o o f 2 Abstract(Chymo)trypsin-like serine fold proteases belong to the serine/cysteine proteases found in eukaryotes, prokaryotes, and viruses. Their catalytic activity is carried out using a triad of amino acids, a nucleophile, a base, and an acid. For this superfamily of proteases, we propose the existence of a universal 3D structure comprising 11 amino acids near the catalytic nucleophile and base -Nucleophile-Base Catalytic Zone (NBCZone). The comparison of NBCZones among 169 eukaryotic, prokaryotic, and viral (chymo)trypsin-like proteases suggested the existence of 15 distinct groups determined by the combination of amino acids located at two "key" structure-functional positions 54 T and 55 T near the catalytic base His57 T .Most eukaryotic and prokaryotic proteases fell into two major groups, [ST]A and TN.Usually, proteases of [ST]A group contain a disulfide bond between cysteines Cys42 T and Cys58 T of the NBCZone. In contrast, viral proteases were distributed among seven groups, and lack this disulfide bond. Furthermore, only the [ST]A group of eukaryotic proteases contains glycine at position 43 T , which is instrumental for activation of these enzymes. In contrast, due to the side chains of residues at position 43 T prokaryotic and viral proteases do not have the ability to carry out the structural transition of the eukaryotic zymogen-zyme type. Journal Pre-proof J o u r n a l P r e -p r o o f pattern G-[DE]-S-G-[GS] (https://prosite.expasy.org/; PROSITE documentation PDOC00124; TRYPSIN_SER, PS00135 [8]). In addition to this pattern, there is also a histidine active site pattern [LIVM]-[ST]-A-[STAG]-H-C (TRYPSIN_HIS, PS00134). In both families, the oxyanion hole is situated adjacent to the nucleophile and is mainly shaped by the main-chain nitrogen atoms of two residues, but again the sequential order is different. Knowing the importance of the existence of a catalytic acid, nucleophile, and oxyanion zones for the function of the α/β hydrolases fold enzymes and with the possible presence of similar structural formations in other types of hydrolases, we carried out a detailed analysis of the spatial structures of (chymo)trypsin-like serine fold prot...

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Section: Nucleophile-base Catalytic Zone (Nbczone) Of Trypsinsupporting

confidence: 57%

Section: Nucleophile-base Catalytic Zone (Nbczone) Of Trypsinmentioning

confidence: 99%

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NBCZone: Universal three-dimensional construction of eleven amino acids near the catalytic nucleophile and base in the superfamily of (chymo)trypsin-like serine fold proteases

Denesyuk

Johnson

Salo‐Ahen

et al. 2020

International Journal of Biological Macromolecules

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“…In our study the most promising markers with the highest correlation between pig model and patient data were directly related to migration and proliferation of epidermal cells (ZYX, IQGA1) and dermal fibroblasts (HtrA1) and thus primary indicators of these processes. Although HtrA1 is a classically secreted protein (Zurawa-Janicka et al, 2017), both ZYX and IQGA1 are mainly associated with cytoskeletal structures and described to exert intracellular functions (Smith et al, 2014;Watanabe et al, 2015). Therefore, their identification might be restricted to exudates collected from NPWT foams with cellular infiltrates releasing high numbers of intracellular proteins.…”

Section: Discussionmentioning

confidence: 99%

Comparative Degradomics of Porcine and Human Wound Exudates Unravels Biomarker Candidates for Assessment of Wound Healing Progression in Trauma Patients

Sabino

Egli

Savickas

et al. 2018

Journal of Investigative Dermatology

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Impaired cutaneous wound healing is a major complication in elderly people and patients suffering from diabetes, the rate of which is rising in industrialized countries. Heterogeneity of clinical manifestations hampers effective molecular diagnostics and decisions for appropriate therapeutic regimens. Using a customized positional quantitative proteomics workflow, we have established a time-resolved proteome and N-terminome resource from wound exudates in a clinically relevant pig wound model that we exploited as a robust template to interpret a heterogeneous dataset from patients undergoing the same wound treatment. With zyxin, IQGA1, and HtrA1, this analysis and validation by targeted proteomics identified differential abundances and proteolytic processing of proteins of epidermal and dermal origin as prospective biomarker candidates for assessment of critical turning points in wound progression. Thus, we show the possibility of using a fine-tuned animal wound model to bridge the translational gap as a prerequisite for future extended clinical studies with large cohorts of individuals affected by healing impairments. Data are available via ProteomeXchange with identifier PXD006674.

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“…Bacterial and mammalian HtrA genes share common structural features with a highly conserved trypsin‐like serine protease domain and one or two PDZ domains at the carboxyl terminus. Different from other HtrA family proteins, human HTRA1, 3 and 4 consist of an amine terminal (N‐terminal) signal peptide, an IGFBP domain, PDZ domain and a Kazal domain (Figure ) …”

Section: Gene Analysis Molecular Structure and Function Of Htra1mentioning

confidence: 99%

Molecular structure and the role of high‐temperature requirement protein 1 in skeletal disorders and cancers

Yuan

Rothzerg

et al. 2019

Cell Proliferation

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Human high‐temperature requirement protein 1 (HTRA1) is a member of serine proteases and consists of four well‐defined domains—an IGFBP domain, a Kazal domain, a protease domain and a PDZ domain. HTRA1 is a secretory protein and also present intracellularly and associated with microtubules. HTRA1 regulates a broad range of physiological processes via its proteolytic activity. This review examines the role of HTRA1 in bone biology, osteoarthritis, intervertebral disc (IVD) degeneration and tumorigenesis. HTRA1 mediates diverse pathological processes via a variety of signalling pathways, such as TGF‐β and NF‐κB. The expression of HTRA1 is increased in arthritis and IVD degeneration, suggesting that HTRA1 protein is attributed to cartilage degeneration and disease progression. Emerging evidence also suggests that HTRA1 has a role in tumorigenesis. Further understanding the mechanisms by which HTRA1 displays as an extrinsic and intrinsic regulator in a cell type–specific manner will be important for the development of HTRA1 as a therapeutic target.

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Structural insights into the activation mechanisms of human HtrA serine proteases

Cited by 66 publications

References 141 publications

NBCZone: Universal three-dimensional construction of eleven amino acids near the catalytic nucleophile and base in the superfamily of (chymo)trypsin-like serine fold proteases

NBCZone: Universal three-dimensional construction of eleven amino acids near the catalytic nucleophile and base in the superfamily of (chymo)trypsin-like serine fold proteases

Comparative Degradomics of Porcine and Human Wound Exudates Unravels Biomarker Candidates for Assessment of Wound Healing Progression in Trauma Patients

Molecular structure and the role of high‐temperature requirement protein 1 in skeletal disorders and cancers

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