EzCatDB: D00429
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DB codeD00429
RLCP classification1.13.30000.10 : Hydrolysis
CATH domainDomain 12.40.10.10 : Thrombin, subunit HCatalytic domain
Domain 22.40.10.10 : Thrombin, subunit HCatalytic domain
E.C.3.4.21.46

CATH domainRelated DB codes (homologues)
2.40.10.10 : Thrombin, subunit HM00139,D00214,M00167,D00426,M00133,D00428,D00430,D00431,D00432,D00433,D00434,D00435,M00227,M00209,D00194,D00197,D00211,D00212,D00216,M00212,D00224,D00497,M00217,M00216,D00528,D00848,D00850,D00851,D00852,D00855,M00152,M00155,M00157,M00181,M00315,M00316,M00317,M00348,M00349,T00074,T00410,T00411

Enzyme Name
UniProtKBKEGG

P00746
Protein nameComplement factor Dcomplement factor D
C3 proactivator convertase
properdin factor D esterase
factor D
factor D (complement)
SynonymsEC 3.4.21.46
C3 convertase activator
Properdin factor D
Adipsin
RefSeqNP_001919.2 (Protein)
NM_001928.2 (DNA/RNA sequence)
MEROPSS01.191 (Serine)
PfamPF00089 (Trypsin)
[Graphical view]


UniProtKB:Accession NumberP00746
Entry nameCFAD_HUMAN
ActivitySelective cleavage of Arg-|-Lys bond in complement factor B when in complex with complement subcomponent C3b or with cobra venom factor.
Subunit
Subcellular locationSecreted.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idL00079L00090L00081C00001L00089I00087I00085I00086
CompoundComplement component C3bCobra venom factorComplement factor BH2OC3 convertase (EzCatDB M00317)Peptidyl-Ser-tetrahedral-intermediate (with previous peptide)Acyl-enzyme(Peptidyl-Ser-acyl group)Peptidyl-Ser-tetrahedral-intermediate
Typepeptide/proteinpeptide/proteinpeptide/proteinH2Opeptide/protein


ChEBI


15377




PubChem


962
22247451




                
1bioA01UnboundUnboundUnbound UnboundUnboundIntermediate-analogue:SOAUnbound
1dfpA01UnboundUnboundUnbound UnboundTransition-state-analogue:DFPUnboundUnbound
1dfpB01UnboundUnboundUnbound UnboundTransition-state-analogue:DFPUnboundUnbound
1dicA01UnboundUnboundUnbound UnboundUnboundIntermediate-analogue:DIC-__OUnbound
1dstA01UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1dsuA01UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1dsuB01UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1fdpA01UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1fdpB01UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1fdpC01UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1fdpD01UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1hfdA01UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1bioA02UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1dfpA02UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1dfpB02UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1dicA02UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1dstA02UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1dsuA02UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1dsuB02UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1fdpA02UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1fdpB02UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1fdpC02UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1fdpD02UnboundUnboundUnbound UnboundUnboundUnboundUnbound
1hfdA02UnboundUnboundUnbound UnboundUnboundUnboundUnbound

Active-site residues
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
1bioA01SER 195
GLY 193;SER 195
 
1dfpA01SER 195
GLY 193;SER 195
 
1dfpB01SER 195
GLY 193;SER 195
 
1dicA01SER 195
GLY 193;SER 195
 
1dstA01SER 195
GLY 193;SER 195
mutant T214S, S215W
1dsuA01SER 195
GLY 193;SER 195
 
1dsuB01SER 195
GLY 193;SER 195
 
1fdpA01SER 195
GLY 193;SER 195
invisible 144-151
1fdpB01SER 195
GLY 193;SER 195
invisible 143-151, 187-192, 217-222
1fdpC01SER 195
       ;SER 195
invisible 144-152, 187-193, 216-222
1fdpD01SER 195
       ;SER 195
invisible 144-151, 187-193, 217-223
1hfdA01SER 195
GLY 193;SER 195
 
1bioA02HIS 57;ASP 102
 
 
1dfpA02HIS 57;ASP 102
 
 
1dfpB02HIS 57;ASP 102
 
 
1dicA02HIS 57;ASP 102
 
 
1dstA02HIS 57;ASP 102
 
mutant S94Y
1dsuA02HIS 57;ASP 102
 
 
1dsuB02HIS 57;ASP 102
 
 
1fdpA02HIS 57;ASP 102
 
 
1fdpB02HIS 57;ASP 102
 
 
1fdpC02HIS 57;ASP 102
 
 
1fdpD02HIS 57;ASP 102
 
 
1hfdA02HIS 57;ASP 102
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[9]p.556-558
[12]


references
[1]
PubMed ID2023254
JournalJ Mol Biol
Year1991
Volume219
Pages1-3
AuthorsNarayana SV, Kilpatrick JM, el-Kabbani O, Babu YS, Bugg CE, Volanakis JE, DeLucas LJ
TitleCrystallization and preliminary X-ray investigation of factor D of human complement.
[2]
PubMed ID8216203
JournalBiochem J
Year1993
Volume295
Pages109-14
AuthorsPerkins SJ, Smith KF
TitleIdentity of the putative serine-proteinase fold in proteins of the complement system with nine relevant crystal structures.
[3]
PubMed ID8216242
JournalBiochem J
Year1993
Volume295
Pages87-99
AuthorsPerkins SJ, Smith KF, Kilpatrick JM, Volanakis JE, Sim RB
TitleModelling of the serine-proteinase fold by X-ray and neutron scattering and sedimentation analyses: occurrence of the fold in factor D of the complement system.
[4]
PubMed ID7981199
JournalBiochemistry
Year1994
Volume33
Pages14393-9
AuthorsKim S, Narayana SV, Volanakis JE
TitleMutational analysis of the substrate binding site of human complement factor D.
[5]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID94118317
PubMed ID8289289
JournalJ Mol Biol
Year1994
Volume235
Pages695-708
AuthorsNarayana SV, Carson M, el-Kabbani O, Kilpatrick JM, Moore D, Chen X, Bugg CE, Volanakis JE, DeLucas LJ
TitleStructure of human factor D. A complement system protein at 2.0 A resolution.
Related PDB1dsu
Related UniProtKBP00746
[6]
PubMed ID8289314
JournalJ Mol Biol
Year1994
Volume235
Pages1144-6
AuthorsNarayana SV, Yamauchi Y, Macon KJ, Moore D, DeLucas LJ, Volanakis JE
TitlePreliminary crystallographic studies on human complement pro-factor D.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID96025834
PubMed ID7592653
JournalJ Biol Chem
Year1995
Volume270
Pages24399-405
AuthorsKim S, Narayana SV, Volanakis JE
TitleCrystal structure of a complement factor D mutant expressing enhanced catalytic activity.
Related PDB1dst
Related UniProtKBP00746
[8]
PubMed ID7751649
JournalJ Immunol
Year1995
Volume154
Pages6073-9
AuthorsKim S, Narayana SV, Volanakis JE
TitleCatalytic role of a surface loop of the complement serine protease factor D.
[9]
PubMed ID8845746
JournalProtein Sci
Year1996
Volume5
Pages553-64
AuthorsVolanakis JE, Narayana SV
TitleComplement factor D, a novel serine protease.
[10]
CommentsX-ray crystallography
JournalActa Crystallogr D Biol Crystallogr
Year1997
Volume53
Pages143-150
AuthorsCole LB, Chu N, Kilpatrick JM, Volanakis JE, Narayana SV, Babu YS
TitleStructure of Diisopropyl Fluorophosphate-Inhibited Factor D.
Related PDB1dfp
[11]
CommentsX-ray crystallography
PubMed ID9757085
JournalActa Crystallogr D Biol Crystallogr
Year1998
Volume54
Pages711-7
AuthorsCole LB, Kilpatrick JM, Chu N, Babu YS
TitleStructure of 3,4-dichloroisocoumarin-inhibited factor D.
Related PDB1dic
[12]
CommentsX-ray crystallography
PubMed ID9753554
JournalJ Mol Biol
Year1998
Volume282
Pages1061-81
AuthorsJing H, Babu YS, Moore D, Kilpatrick JM, Liu XY, Volanakis JE, Narayana SV
TitleStructures of native and complexed complement factor D: implications of the atypical His57 conformation and self-inhibitory loop in the regulation of specific serine protease activity.
Related PDB1bio,1hfd
[13]
PubMed ID10052957
JournalBiochemistry
Year1999
Volume38
Pages2849-59
AuthorsTaylor FR, Bixler SA, Budman JI, Wen D, Karpusas M, Ryan ST, Jaworski GJ, Safari-Fard A, Pollard S, Whitty A
TitleInduced fit activation mechanism of the exceptionally specific serine protease, complement factor D.
[14]
CommentsX-ray crystallography
PubMed ID10022823
JournalEMBO J
Year1999
Volume18
Pages804-14
AuthorsJing H, Macon KJ, Moore D, DeLucas LJ, Volanakis JE, Narayana SV
TitleStructural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D.
Related PDB1fdp
[15]
PubMed ID11414354
JournalImmunol Rev
Year2001
Volume180
Pages123-35
AuthorsXu Y, Narayana SV, Volanakis JE
TitleStructural biology of the alternative pathway convertase.
[16]
PubMed ID12080056
JournalJ Biol Chem
Year2002
Volume277
Pages33068-74
AuthorsTurner RB, Liu L, Sazonova IY, Reed GL
TitleStructural elements that govern the substrate specificity of the clot-dissolving enzyme plasmin.

comments
This enzyme belongs to the peptidase family-S1.
Despite the catalytic triad, composed of Ser/His/Asp, its conformation is disrupted, showing lower activity (in terms of kcat), compared to that of trypsin (D00197 in EzCatDB), according to the literature [9]. This disruption of the active-site structure seems to be due to the residues, Ser94/Thr214/Ser215. The triple mutant of S94Y/T214S/S215W gives a similar conformation of the catalytic triad to that of trypsin (see [9]). This literature suggested that substrate-induced (C3b-induced) conformational changes, which can lead to the rearrangement of the catalytic-triad residues, might be necessary for the enzyme activation (see [9], [12] & [13]).
Moreover, this enzyme activates factor B in the alternative pathway of complement system, generating C3-convertase that is complexed with C3b molecule (M00317 in EzCatDB).

createdupdated
2004-10-262012-08-24


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Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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