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PDBsum entry 1fdp
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protein Protein-protein interface(s) links
Hydrolase PDB id
1fdp

 

 

 

 

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Contents
Protein chains
221 a.a. *
201 a.a. *
Waters ×631
* Residue conservation analysis
PDB id:
1fdp
Name: Hydrolase
Title: Proenzyme of human complement factor d, recombinant profactor d
Structure: Proenzyme of complement factor d. Chain: a, b, c, d. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell: sf9.
Resolution:
2.10Å     R-factor:   0.204     R-free:   0.251
Authors: H.Jing,K.J.Macon,D.Moore,L.J.Delucas,J.E.Volanakis,S.V.L.Narayana
Key ref:
H.Jing et al. (1999). Structural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D. EMBO J, 18, 804-814. PubMed id: 10022823 DOI: 10.1093/emboj/18.4.804
Date:
03-Dec-98     Release date:   03-Dec-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00746  (CFAD_HUMAN) -  Complement factor D from Homo sapiens
Seq:
Struc: 		253 a.a.
221 a.a.
Protein chains
Pfam   ArchSchema ?
P00746  (CFAD_HUMAN) -  Complement factor D from Homo sapiens
Seq:
Struc: 		253 a.a.
201 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D: E.C.3.4.21.46  - complement factor D.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Cleaves component factor B (Arg-|-Lys) when in complex with C3b or with cobra venom factor (CVF).

 

 
DOI no: 10.1093/emboj/18.4.804 EMBO J 18:804-814 (1999)
PubMed id: 10022823  
 
 
Structural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D.
H.Jing, K.J.Macon, D.Moore, L.J.DeLucas, J.E.Volanakis, S.V.Narayana.
 
  ABSTRACT  
 
The crystal structure of profactor D, determined at 2.1 A resolution with an Rfree and an R-factor of 25.1 and 20.4%, respectively, displays highly flexible or disordered conformation for five regions: N-22, 71-76, 143-152, 187-193 and 215-223. A comparison with the structure of its mature serine protease, complement factor D, revealed major conformational changes in the similar regions. Comparisons with the zymogen-active enzyme pairs of chymotrypsinogen, trypsinogen and prethrombin-2 showed a similar distribution of the flexible regions. However, profactor D is the most flexible of the four, and its mature enzyme displays inactive, self-inhibited active site conformation. Examination of the surface properties of the N-terminus-binding pocket indicates that Ile16 may play the initial positioning role for the N-terminus, and Leu17 probably also helps in inducing the required conformational changes. This process, perhaps shared by most chymotrypsinogen-like zymogens, is followed by a factor D-unique step, the re-orientation of an external Arg218 to an internal position for salt-bridging with Asp189, leading to the generation of the self-inhibited factor D.
 
  Selected figure(s)  
 
Figure 3.
Figure 3 Stereo view of the overall and active site conformations of PFD in comparison with FD. (A) Overall structure and (B) active site. Molecule A of PFD is shaded and FD is not shaded. The figure was prepared using RIBBONS (Carson, 1997). 		Figure 4.
Figure 4 Comparisons of four zymogen–enzyme pairs. (A) High B-factor regions in PFD, chymotrypsinogen (2CGA-A), trypsinogen (2TGT) and prethrombin-2 (1HAG). From low to high B-factors are shown in cyan, green, yellow, orange, red and white. This panel was prepared using RIBBONS (Carson, 1997). (B) Surface charge of the N-terminus-binding pockets in PFD–FD and trypsinogen–trypsin. Residues 16–25 of the mature enzymes are shown in ball-and-stick model and are excluded in the surface calculations. They are superimposed onto the surface of the zymogens based on structural alignments. This panel was prepared using GRASP (Nicolls et al., 1991).
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1999, 18, 804-814) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference Google scholar

  PubMed id Reference
21205667 F.Forneris, D.Ricklin, J.Wu, A.Tzekou, R.S.Wallace, J.D.Lambris, and P.Gros (2010).
Structures of C3b in complex with factors B and D give insight into complement convertase formation.
  Science, 330, 1816-1820.
PDB codes: 2xw9 2xwa 2xwb 2xwj
17317663 M.J.Gorman, Y.Wang, H.Jiang, and M.R.Kanost (2007).
Manduca sexta hemolymph proteinase 21 activates prophenoloxidase-activating proteinase 3 in an insect innate immune response proteinase cascade.
  J Biol Chem, 282, 11742-11749.  
17287215 S.Piao, S.Kim, J.H.Kim, J.W.Park, B.L.Lee, and N.C.Ha (2007).
Crystal structure of the serine protease domain of prophenoloxidase activating factor-I.
  J Biol Chem, 282, 10783-10791.
PDB code: 2olg
18516248 G.H.Caughey (2006).
A Pulmonary Perspective on GASPIDs: Granule-Associated Serine Peptidases of Immune Defense.
  Curr Respir Med Rev, 2, 263-277.  
16807918 K.Segers, J.Rosing, and G.A.Nicolaes (2006).
Structural models of the snake venom factor V activators from Daboia russelli and Daboia lebetina.
  Proteins, 64, 968-984.
PDB codes: 2fjo 2fjq
15578663 O.Guvench, D.J.Price, and C.L.Brooks (2005).
Receptor rigidity and ligand mobility in trypsin-ligand complexes.
  Proteins, 58, 407-417.  
14679197 S.Prasad, A.M.Cantwell, L.A.Bush, P.Shih, H.Xu, and E.Di Cera (2004).
Residue Asp-189 controls both substrate binding and the monovalent cation specificity of thrombin.
  J Biol Chem, 279, 10103-10108.  
14656436 G.P.Pal, T.De Veyra, J.S.Elce, and Z.Jia (2003).
Crystal structure of a micro-like calpain reveals a partially activated conformation with low Ca2+ requirement.
  Structure, 11, 1521-1526.
PDB code: 1qxp
12384499 C.Hink-Schauer, E.Estébanez-Perpiñá, E.Wilharm, P.Fuentes-Prior, W.Klinkert, W.Bode, and D.E.Jenne (2002).
The 2.2-A crystal structure of human pro-granzyme K reveals a rigid zymogen with unusual features.
  J Biol Chem, 277, 50923-50933.
PDB codes: 1mza 1mzd
11823416 M.Budayova-Spano, M.Lacroix, N.M.Thielens, G.J.Arlaud, J.C.Fontecilla-Camps, and C.Gaboriaud (2002).
The crystal structure of the zymogen catalytic domain of complement protease C1r reveals that a disruptive mechanical stress is required to trigger activation of the C1 complex.
  EMBO J, 21, 231-239.
PDB code: 1gpz
12429092 M.Budayova-Spano, W.Grabarse, N.M.Thielens, H.Hillen, M.Lacroix, M.Schmidt, J.C.Fontecilla-Camps, G.J.Arlaud, and C.Gaboriaud (2002).
Monomeric structures of the zymogen and active catalytic domain of complement protease c1r: further insights into the c1 activation mechanism.
  Structure, 10, 1509-1519.
PDB codes: 1md7 1md8
11470437 C.Eigenbrot, D.Kirchhofer, M.S.Dennis, L.Santell, R.A.Lazarus, J.Stamos, and M.H.Ultsch (2001).
The factor VII zymogen structure reveals reregistration of beta strands during activation.
  Structure, 9, 627-636.
PDB code: 1jbu
11168406 R.Egelund, T.E.Petersen, and P.A.Andreasen (2001).
A serpin-induced extensive proteolytic susceptibility of urokinase-type plasminogen activator implicates distortion of the proteinase substrate-binding pocket and oxyanion hole in the serpin inhibitory mechanism.
  Eur J Biochem, 268, 673-685.  
10775260 C.Gaboriaud, V.Rossi, I.Bally, G.J.Arlaud, and J.C.Fontecilla-Camps (2000).
Crystal structure of the catalytic domain of human complement c1s: a serine protease with a handle.
  EMBO J, 19, 1755-1765.
PDB code: 1elv
10637221 H.Jing, Y.Xu, M.Carson, D.Moore, K.J.Macon, J.E.Volanakis, and S.V.Narayana (2000).
New structural motifs on the chymotrypsin fold and their potential roles in complement factor B.
  EMBO J, 19, 164-173.
PDB code: 1dle
10708950 K.M.Mulder (2000).
Role of Ras and Mapks in TGFbeta signaling.
  Cytokine Growth Factor Rev, 11, 23-35.  
10617628 Y.Xu, A.Circolo, H.Jing, Y.Wang, S.V.Narayana, and J.E.Volanakis (2000).
Mutational analysis of the primary substrate specificity pocket of complement factor B. Asp(226) is a major structural determinant for p(1)-Arg binding.
  J Biol Chem, 275, 378-385.  
10601010 C.M.Hosfield, J.S.Elce, P.L.Davies, and Z.Jia (1999).
Crystal structure of calpain reveals the structural basis for Ca(2+)-dependent protease activity and a novel mode of enzyme activation.
  EMBO J, 18, 6880-6889.
PDB code: 1df0
  10551898 S.R.Barnum (1999).
Inhibition of complement as a therapeutic approach in inflammatory central nervous system (CNS) disease.
  Mol Med, 5, 569-582.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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