A dysfunctional Cl inhibitor protein with a new reactive center mutation (Arg‐444→Leu)

@article{Frangi1992ADC,
  title={A dysfunctional Cl inhibitor protein with a new reactive center mutation (Arg‐444→Leu)},
  author={Donatella Frangi and Kulwant Singh Aulak and Marco Cicardi and Richard A. Harrison and Alvin E. Davis},
  journal={FEBS Letters},
  year={1992},
  volume={301}
}
A Pl mutation (Arg‐444→Leu) was identified in a dysfunctional Cl inhibitor from a patient with type 2 hereditary angioneurotic edema. The mutation was defined at the level of the protein (by sequence analysis of the Pseudomonas aeruginosa elastase‐derived reactive center peptide), and the mRNA (CGC→CTC) (by sequence analysis of PCR‐amplified DNA). 
25 Citations
A Mutation Unique in Serine Protease Inhibitors (Serpins) Identified in a Family with Type II Hereditary Angioneurotic Edema
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This work reports the first molecular defect characterized in a Spanish family with type II HANE, and to date, this is the first reported mutation at the P-1′ site of the reactive center in individuals with type Two HANE.
Normal C1 inhibitor mRNA expression level in type I hereditary angioedema patients: newly found C1 inhibitor gene mutations
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This data indicates that mutations in this gene cause a decreased level of antigenic or functional C1INH in patients with type I hereditary angioedema or functional HAE.
A review of the reported defects in the human C1 esterase inhibitor gene producing hereditary angioedema including four new mutations.
TLDR
The DNA from HAE patients is sequenced and four previously unreported mutations are discovered, including a splice site error and a missense error present in the eighth exon of the C1INH.
Mechanisms of C1-inhibitor deficiency.
TLDR
Based on studies in deficient patients, C1-Inh appears pivotal in regulating the activation of complement classical pathway and of contact system, and candidate mediator of angioedema is bradykinin, a potent vasoactive peptide, released upon contact system activation.
What do dysfunctional serpins tell us about molecular mobility and disease?
TLDR
Comparisons of dysfunctional variants and crystal structures of serpins in different forms provide insights into the molecular functions and remarkable folding properties of this family and define the domains which control this folding and show how spontaneous but inappropriate changes in conformation cause diverse diseases.
Unique C1 inhibitor dysfunction in a kindred without angioedema. II. Identification of an Ala443-->Val substitution and functional analysis of the recombinant mutant protein.
TLDR
The Ala443-->Val mutation converts C1 inhibitor from a substrate to an inhibitor of trypsin, and the role of the P2 residue in the determination of target protease specificity is emphasized.
Detection of C1 inhibitor mutations in patients with hereditary angioedema.
TLDR
Single-stranded conformational polymorphism is an effective approach for identifying new mutations in HAE, and is important for both defining which residues are required for C1 inhibitor secretion or function and providing the basis for future studies to define the relationship between the C1 inhibitors genotype and disease severity.
Crucial residues in the carboxy-terminal end of C1 inhibitor revealed by pathogenic mutants impaired in secretion or function.
TLDR
Data point to a key role of certain residues in the conserved COOH-terminal region of serpins in determining the protein foldings compatible with transport and proper exposure of the reactive site loop in angioedema patients.
Structure and function of C1-inhibitor.
C1-INH belongs to the family of serpins. Structural studies have yielded a clear understanding of the biochemical principle underlying the functional activities of these proteins. Although the
C1-inhibitor deficiency and angioedema.
TLDR
Effective therapies can prevent or revert angioedema symptoms in C1-Inh deficiency, the main problem of this condition remaining misdiagnosis.
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References

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TLDR
This substitution is compatible with a point mutation of the 444Arg codon (CGC→AGC), and represents the first non‐histidine, non‐cysteine P1 residue mutant described for C1 inhibitor.
Dysfunctional C1-inhibitor(At), isolated from a type II hereditary-angio-oedema plasma, contains a P1 'reactive centre' (Arg444----His) mutation.
Simple rapid procedures for identification and analysis of dysfunctional C1-inhibitor proteins mutated at the reactive-centre P1 residue have been developed and used to define structurally a
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TLDR
The deletion of nucleotides encoding Lys-251 (AAG) in C1 inhibitor Ta, the dysfunctional C1 inhibitors from a family with type II hereditary angioneurotic edema, is described and it is suggested that this deletion creates a new glycosylation site on SDS/PAGE and very likely interferes with protein function.
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TLDR
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TLDR
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TLDR
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TLDR
Southern blot analysis of genomic DNA was performed and it was shown that the three different mutations leading to restriction fragment length polymorphism (RFLP) are located in the same region of the C1-INH gene.
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Limited proteolysis of C1 inhibitor (C1-INH) by neutrophil elastase, Pseudomonas elastase and snake venoms resulted in initial cleavage within the molecule's N-terminus followed by further cleavage
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