Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Factor V (FV) is a large (2,196 amino acids) nonenzymatic cofactor in the coagulation cascade with a domain organization (A1-A2-B-A3-C1-C2) similar to the one of factor VIII (FVIII). FV is activated to factor Va (FVa) by thrombin, which cleaves away the B domain leaving a heterodimeric structure composed of a heavy chain (A1-A2) and a light chain (A3-C1-C2). Activated protein C (APC), together with its cofactor protein S (PS), inhibits the coagulation cascade via limited proteolysis of FVa and FVIIIa (APC cleaves FVa at residues R306, R506, and R679). The A domains of FV and FVIII share important sequence identity with the plasma copper-binding protein ceruloplasmin (CP). The X-ray structure of CP and theoretical models for FVIII have been recently reported. This information allowed us to build a theoretical model (994 residues) for the A domains of human FV/FVa (residues 1-656 and 1546-1883). Structural analysis of the FV model indicates that: (a) the three A domains are arranged in a triangular fashion as in the case of CP and the organization of these domains should remain essentially the same before and after activation; (b) a Type II copper ion is located at the A1-A3 interface; (c) residues R306 and R506 (cleavage sites for APC) are both solvent exposed; (d) residues 1667-1765 within the A3 domain, expected to interact with the membrane, are essentially buried; (e) APC does not bind to FVa residues 1865-1874. Several other features of factor V/Va, like the R506Q and A221V mutations; factor Xa (FXa) and human neutrophil elastase (HNE) cleavages; protein S, prothrombin and FXa binding, are also investigated.
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PMID:Structural investigation of the A domains of human blood coagulation factor V by molecular modeling. 965 35

Protein and peptide S-nitrosothiols (SNOs) are involved in guanylate cyclase-independent signaling associated with nitric oxide synthase (NOS) activation. As a general rule, SNO formation requires the presence of an electron acceptor such as Cu2+. Various proteins have been identified that catalyze SNO formation, including NOS itself, ceruloplasmin, and hemoglobin. Biochemical evidence suggests the existence of other SNO synthases and NOS-associated proteins involved in SNO formation following NOS activation. Indeed, both hydrophilic and hydrophobic consensus motifs have been identified that favor protein S-nitrosylation. Inorganic SNO formation appears also to occur in biological systems at low pH levels and/or in membranes. Once formed, SNOs localized to specific cellular compartments signal specific effects, ranging from gene regulation to ion channel gating. Indeed, the number of cellular and physiological functions appreciated to be regulated through SNO synthesis, localization, and catabolism is increasing. Although research into SNO biosynthesis is in its infancy, the importance of this field of biochemistry has been confirmed repeatedly by investigators from a broad spectrum of disciplines.
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PMID:S-nitrosothiol formation. 1629 Dec 25