4kkd

The X-ray crystal structure of Mannose-binding lectin-associated serine proteinase-3 reveals the structural basis for enzyme inactivity associated with the 3MC syndromeThe X-ray crystal structure of Mannose-binding lectin-associated serine proteinase-3 reveals the structural basis for enzyme inactivity associated with the 3MC syndrome

Structural highlights 4kkd is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5991Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease MASP1_HUMAN Defects in MASP1 are the cause of 3MC syndrome type 1 (3MC1) [MIM:257920. 3MC1 is a disorder characterized by facial dysmorphism that includes hypertelorism, blepharophimosis, blepharoptosis and highly arched eyebrows, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. The term 3MC syndrome includes Carnevale, Mingarelli, Malpuech, and Michels syndromes. Function MASP1_HUMAN Functions in the lectin pathway of complement, which performs a key role in innate immunity by recognizing pathogens through patterns of sugar moieties and neutralizing them. The lectin pathway is triggered upon binding of mannan-binding lectin (MBL) and ficolins to sugar moieties which leads to activation of the associated proteases MASP1 and MASP2. Functions as an endopeptidase and may activate MASP2 or C2 or directly activate C3 the key component of complement reaction. Isoform 2 may have an inhibitory effect on the activation of the lectin pathway of complement or may cleave IGFBP5. Publication Abstract from PubMed The mannose-binding lectin associated-protease-3 (MASP-3) is a member of the lectin pathway of the complement system, a key component of human innate and active immunity. Mutations in MASP-3 have recently been found to be associated with Carnevale, Mingarelli, Malpuech and Michels (3MC) syndrome, a severe developmental disorder manifested by cleft palate, intellectual disability and skeletal abnormalities. However, the molecular basis for MASP-3 function remains to be understood. Here we characterise the substrate specificity of MASP-3 by screening against a combinatorial peptide substrate library. Through this approach, we successfully identified a peptide substrate that was 20-fold more efficiently cleaved than any other identified to date. Further, we demonstrated that mutant forms of the enzyme associated with 3MC syndrome were completely inactive against this substrate. To address the structural basis for this defect, we determined the 2.6 angstrom structure of the zymogen form of the G666E mutant of MASP-3. These data reveal that the mutation disrupts the active site and perturbs the position of the catalytic serine residue. Together, these insights into the function of MASP-3 reveal how a mutation in this enzyme causes it to be inactive and thus contribute to the 3MC syndrome. The X-ray crystal structure of Mannose-binding lectin-associated serine proteinase-3 reveals the structural basis for enzyme inactivity associated with the 3MC syndrome.,Yongqing T, Wilmann PG, Reeve SB, Coetzer TH, Smith AI, Whisstock JC, Pike RN, Wijeyewickrema LC J Biol Chem. 2013 Jun 21. PMID:23792966 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Mannan-binding lectin serine protease

spinqualitylabelsall models 4kkd, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image