C1r Enzyme

Product List Background C1r Enzyme Functional Service
Specie Reactivity Human
Type Native Protein
Applications Functional Assays


Background

It is well known that C1 is a crucial initiator of the classical complement pathway, while the C1r enzyme (C1R) is an integral part of C1. C1R, also known as complement C1r, EDSPD1, and EDS8, is a vital member of the S1 family of peptidases. C1r enzyme is known to be the activated form of C1r zymogen and is inactive before C1 is activated.

Its Gene ID: 715, UniProtKB ID: P00736, and OMIM ID: 613785.

Description of C1r Enzyme

The C1 complex is composed of one C1q molecule, two C1r molecules, and two C1s molecules. Generally, when C1q binds to the immune complex, a specific stimulation signal is generated. This signal promotes the conversion of the C1r proenzyme into the C1r enzyme. Subsequently, the generated C1r enzyme can stimulate and activate C1s, converting C1s proenzyme into C1s enzyme, thereby initiating the classical complement pathway.

Fig.1 C1r structure. (Gál, et al., 2009) Fig.1 Structure of the catalytic region of active C1r.1,3

Properties of C1r Enzyme

The C1r zymogen is reportedly highly susceptible to external factors, which allows for its spontaneous activation under normal conditions. Once activated, C1r zymogen transforms into the C1r enzyme, characterized by a distinctive double-stranded structure. Furthermore, this enzyme comprises two distinct domains, namely the C-terminal catalytic domain and the N-terminal domain, each serving different functions. Specifically, the C-terminal domain primarily facilitates C1r activation and the proteolysis of C1s, while the N-terminal domain is involved in the formation of the C1 complex.

Functions

The C1r enzyme plays a crucial role in activating the C1s proenzyme. The C1r enzyme facilitates the activation of two C1s proenzymes to generate C1s enzymes. Subsequently, two C1r enzyme molecules bind to the two C1s molecules to form a complex. Finally, this complex binds to C1q to produce a fully active C1 molecule. In the presence of activating factors, the C1 molecule initiates the complement cascade by activating other complement factors.

C1r Enzyme Assays

Typically, C1r enzyme activity can be characterized by monitoring the ability of the C1r enzyme to covalently bind to a C1 esterase inhibitor.

As your loyal partner in complement research, Creative Biolabs is willing to provide products related to complement projects, such as Native Human Complement C1r Enzyme Protein. Please contact our complement experts to develop a feasible plan for you.


C1r Enzyme Functional Service

Creative Biolabs provides a comprehensive range of C1r enzyme related products, including native human complement C1r enzyme protein. These products can effectively carry out C1r enzyme related experiments and thus play an important role in your research.

Fig. 2 Statistics of the binding response of different compounds to C1r. Fig. 2 The binding response of different compounds to C1r.2,3

Compared to other complement targets, the development of C1r-targeted therapeutics is currently underdeveloped. Researchers have introduced an innovative fragment-based drug discovery method that combines surface plasmon resonance (SPR) with molecular modeling techniques.2,3 This approach is designed to identify and characterize new small molecule fragments that have the potential to bind effectively to the C1r protein. This study reports the identification of 24 new small molecule fragments that directly interact with C1r, which is the initiating protease of the classical pathway of the complement system. Among these fragments, two have been identified as CMP-1611 and CMP-1696. These two fragments inhibit the classical pathway but exhibit different selectivities. Several of these compounds may represent significant research tools and hold promise as innovative therapeutic options.

Creative Biolabs offers C1r enzyme functional services, including detection of C1r enzyme binding and other tailored functional services for our esteemed clients engaged in clinical and scientific research.

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References

  1. Gál, Péter, et al. "Early complement proteases: C1r, C1s and MASPs. A structural insight into activation and functions." Molecular immunology 46.14 (2009): 2745-2752.
  2. Rushing, Blake R., et al. "Targeting the initiator protease of the classical pathway of complement using fragment-based drug discovery." Molecules 25.17 (2020): 4016.
  3. Distributed under Open Access license CC BY 4.0, without modification.
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