1rs0
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Crystal Structure Analysis of the Bb segment of Factor B complexed with Di-isopropyl-phosphate (DIP)
OverviewOverview
The C-terminal fragment, Bb, of factor B combines with C3b to form the, pivotal C3-convertase, C3bBb, of alternative complement pathway. Bb, consists of a von Willebrand factor type A (vWFA) domain that is, structurally similar to the I domains of integrins and a serine protease, (SP) domain that is in inactive conformation. The structure of the C3bBb, complex would be important in deciphering the activation mechanism of the, SP domain. However, C3bBb is labile and not amenable to X-ray diffraction, studies. We engineered a disulfide bond in the vWFA domain of Bb, homologous to that shown to lock I domains in active conformation. The, crystal structures of Bb(C428-C435) and its inhibitor complexes reveal, that the adoption of the "active" conformation by the vWFA domain is not, sufficient to activate the C3-convertase catalytic apparatus and also, provide insights into the possible mode of C3-convertase activation.
DiseaseDisease
Known diseases associated with this structure: Macular degeneration, age-related, reduced risk of OMIM:[138470]
About this StructureAbout this Structure
1RS0 is a Single protein structure of sequence from Homo sapiens with IOD, NA, MG and DFP as ligands. Active as Alternative-complement-pathway C3/C5 convertase, with EC number 3.4.21.47 Full crystallographic information is available from OCA.
ReferenceReference
Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase., Ponnuraj K, Xu Y, Macon K, Moore D, Volanakis JE, Narayana SV, Mol Cell. 2004 Apr 9;14(1):17-28. PMID:15068800
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