DB code: D00429

RLCP classification 1.13.30000.10 : Hydrolysis
CATH domain 2.40.10.10 : Thrombin, subunit H Catalytic domain
2.40.10.10 : Thrombin, subunit H Catalytic domain
E.C. 3.4.21.46
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.40.10.10 : Thrombin, subunit H M00139 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P00746 Complement factor D
EC 3.4.21.46
C3 convertase activator
Properdin factor D
Adipsin
NP_001919.2 (Protein)
NM_001928.2 (DNA/RNA sequence)
S01.191 (Serine)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
complement factor D
C3 proactivator convertase
properdin factor D esterase
factor D
factor D (complement)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00746 CFAD_HUMAN Selective cleavage of Arg-|-Lys bond in complement factor B when in complex with complement subcomponent C3b or with cobra venom factor. Secreted.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id L00079 L00090 L00081 C00001 L00089 I00087 I00085 I00086
E.C.
Compound Complement component C3b Cobra venom factor Complement factor B H2O C3 convertase (EzCatDB M00317) Peptidyl-Ser-tetrahedral-intermediate (with previous peptide) Acyl-enzyme(Peptidyl-Ser-acyl group) Peptidyl-Ser-tetrahedral-intermediate
Type peptide/protein peptide/protein peptide/protein H2O peptide/protein
ChEBI 15377
PubChem 962
22247451
1bioA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:SOA Unbound
1dfpA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Transition-state-analogue:DFP Unbound Unbound
1dfpB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Transition-state-analogue:DFP Unbound Unbound
1dicA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:DIC-__O Unbound
1dstA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dsuA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dsuB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fdpA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fdpB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fdpC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fdpD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hfdA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bioA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dfpA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dfpB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dicA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dstA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dsuA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dsuB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fdpA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fdpB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fdpC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fdpD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hfdA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1bioA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1dfpA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1dfpB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1dicA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1dstA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195 mutant T214S, S215W
1dsuA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1dsuB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1fdpA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195 invisible 144-151
1fdpB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195 invisible 143-151, 187-192, 217-222
1fdpC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 ;SER 195 invisible 144-152, 187-193, 216-222
1fdpD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 ;SER 195 invisible 144-151, 187-193, 217-223
1hfdA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1bioA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1dfpA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1dfpB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1dicA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1dstA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102 mutant S94Y
1dsuA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1dsuB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1fdpA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1fdpB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1fdpC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1fdpD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1hfdA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[9]
p.556-558
[12]

References
[1]
Resource
Comments
Medline ID
PubMed ID 2023254
Journal J Mol Biol
Year 1991
Volume 219
Pages 1-3
Authors Narayana SV, Kilpatrick JM, el-Kabbani O, Babu YS, Bugg CE, Volanakis JE, DeLucas LJ
Title Crystallization and preliminary X-ray investigation of factor D of human complement.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8216203
Journal Biochem J
Year 1993
Volume 295
Pages 109-14
Authors Perkins SJ, Smith KF
Title Identity of the putative serine-proteinase fold in proteins of the complement system with nine relevant crystal structures.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8216242
Journal Biochem J
Year 1993
Volume 295
Pages 87-99
Authors Perkins SJ, Smith KF, Kilpatrick JM, Volanakis JE, Sim RB
Title Modelling 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.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 7981199
Journal Biochemistry
Year 1994
Volume 33
Pages 14393-9
Authors Kim S, Narayana SV, Volanakis JE
Title Mutational analysis of the substrate binding site of human complement factor D.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID 94118317
PubMed ID 8289289
Journal J Mol Biol
Year 1994
Volume 235
Pages 695-708
Authors Narayana SV, Carson M, el-Kabbani O, Kilpatrick JM, Moore D, Chen X, Bugg CE, Volanakis JE, DeLucas LJ
Title Structure of human factor D. A complement system protein at 2.0 A resolution.
Related PDB 1dsu
Related UniProtKB P00746
[6]
Resource
Comments
Medline ID
PubMed ID 8289314
Journal J Mol Biol
Year 1994
Volume 235
Pages 1144-6
Authors Narayana SV, Yamauchi Y, Macon KJ, Moore D, DeLucas LJ, Volanakis JE
Title Preliminary crystallographic studies on human complement pro-factor D.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID 96025834
PubMed ID 7592653
Journal J Biol Chem
Year 1995
Volume 270
Pages 24399-405
Authors Kim S, Narayana SV, Volanakis JE
Title Crystal structure of a complement factor D mutant expressing enhanced catalytic activity.
Related PDB 1dst
Related UniProtKB P00746
[8]
Resource
Comments
Medline ID
PubMed ID 7751649
Journal J Immunol
Year 1995
Volume 154
Pages 6073-9
Authors Kim S, Narayana SV, Volanakis JE
Title Catalytic role of a surface loop of the complement serine protease factor D.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8845746
Journal Protein Sci
Year 1996
Volume 5
Pages 553-64
Authors Volanakis JE, Narayana SV
Title Complement factor D, a novel serine protease.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID
Journal Acta Crystallogr D Biol Crystallogr
Year 1997
Volume 53
Pages 143-150
Authors Cole LB, Chu N, Kilpatrick JM, Volanakis JE, Narayana SV, Babu YS
Title Structure of Diisopropyl Fluorophosphate-Inhibited Factor D.
Related PDB 1dfp
Related UniProtKB
[11]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9757085
Journal Acta Crystallogr D Biol Crystallogr
Year 1998
Volume 54
Pages 711-7
Authors Cole LB, Kilpatrick JM, Chu N, Babu YS
Title Structure of 3,4-dichloroisocoumarin-inhibited factor D.
Related PDB 1dic
Related UniProtKB
[12]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9753554
Journal J Mol Biol
Year 1998
Volume 282
Pages 1061-81
Authors Jing H, Babu YS, Moore D, Kilpatrick JM, Liu XY, Volanakis JE, Narayana SV
Title Structures 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 PDB 1bio 1hfd
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 10052957
Journal Biochemistry
Year 1999
Volume 38
Pages 2849-59
Authors Taylor FR, Bixler SA, Budman JI, Wen D, Karpusas M, Ryan ST, Jaworski GJ, Safari-Fard A, Pollard S, Whitty A
Title Induced fit activation mechanism of the exceptionally specific serine protease, complement factor D.
Related PDB
Related UniProtKB
[14]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10022823
Journal EMBO J
Year 1999
Volume 18
Pages 804-14
Authors Jing H, Macon KJ, Moore D, DeLucas LJ, Volanakis JE, Narayana SV
Title Structural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D.
Related PDB 1fdp
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 11414354
Journal Immunol Rev
Year 2001
Volume 180
Pages 123-35
Authors Xu Y, Narayana SV, Volanakis JE
Title Structural biology of the alternative pathway convertase.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 12080056
Journal J Biol Chem
Year 2002
Volume 277
Pages 33068-74
Authors Turner RB, Liu L, Sazonova IY, Reed GL
Title Structural elements that govern the substrate specificity of the clot-dissolving enzyme plasmin.
Related PDB
Related UniProtKB

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).

Created Updated
2004-10-26 2012-08-24