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PDBsum entry 1rtk
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Hormone/growth factor PDB id
1rtk

 

 

 

 

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Contents
Protein chain
486 a.a. *
Ligands
GBS
Metals
IOD ×2
_NA ×7
_MG
Waters ×272
* Residue conservation analysis
PDB id:
1rtk
Name: Hormone/growth factor
Title: Crystal structure analysis of the bb segment of factor b complexed with 4-guanidinobenzoic acid
Structure: Complement factor b bb fragment. Chain: a. Fragment: complement factor b bb fragment. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cfb, bf, bfd. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: bti-tn-5b1-4. Expression_system_cell: egg. Other_details: sf9 cells were also used
Resolution:
2.30Å     R-factor:   0.208     R-free:   0.245
Authors: K.Ponnuraj,Y.Xu,K.Macon,D.Moore,J.E.Volanakis,S.V.Narayana
Key ref:
K.Ponnuraj et al. (2004). Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase. Mol Cell, 14, 17-28. PubMed id: 15068800 DOI: 10.1016/S1097-2765(04)00160-1
Date:
10-Dec-03     Release date:   14-Dec-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00751  (CFAB_HUMAN) -  Complement factor B from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		764 a.a.
486 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.47  - alternative-complement-pathway C3/C5 convertase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Cleaves C3 in the alpha-chain to yield C3a and C3b. Cleaves C5 in the alpha-chain to yield C5a and C5b. Both cleavages take place at the C-terminal of an arginine residue.

 

 
DOI no: 10.1016/S1097-2765(04)00160-1 Mol Cell 14:17-28 (2004)
PubMed id: 15068800  
 
 
Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase.
K.Ponnuraj, Y.Xu, K.Macon, D.Moore, J.E.Volanakis, S.V.Narayana.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Cartoon Representation of C3-Convertase FormationC3b attached to an activating surface binds factor B, which undergoes conformational changes suitable for the cleavage by factor D, resulting in C3-convertase formation. 		Figure 5.
Figure 5. Structures of Bb^C428-C435 Inhibitor Complexes(A) Superposition of the active sites of Bb^C428-C435 (gold) and Bb^C428-C435-BCX583 (light green) crystal structures. The inhibitor (BCX583) covalently linked to Ser^195 is held in position by hydrogen bonding to Asp^715(226) through a water molecule (lavender). The L2 loop (red) is seen only in the inhibitor complex structure.(B) Comparison of the active sites of Bb^C428-C435-DIP and Bb^C428-C435. The backbone of the inhibitor-bound Bb^C428-C435 is shown in light green color, while the inhibitor-free Bb^C428-C435 is shown in gold color. Covalently bound DIP molecule points its phosphoryl oxygen into the putative oxyanion hole (marked with black star) and forces it to acquire a tight β turn from a zymogen-like 3[10] helix (transparent red color) conformation.(C) Stereo close-up of the superposition of the 670(191)-674(194) segment of Bb^C428-C435 (gold) and Bb^C428-C435-DIP complex (light green). The orientational difference of carbonyl oxygen of the residue 671(192) is indicated in the boxed area.
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2004, 14, 17-28) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21404359 K.Vengadesan, and S.V.Narayana (2011).
Structural biology of gram-positive bacterial adhesins.
  Protein Sci, 20, 759-772.  
20809655 A.D.Vogt, A.Bah, and E.Di Cera (2010).
Evidence of the E*-E equilibrium from rapid kinetics of Na+ binding to activated protein C and factor Xa.
  J Phys Chem B, 114, 16125-16130.  
20467445 D.Serruto, R.Rappuoli, M.Scarselli, P.Gros, and J.A.van Strijp (2010).
Molecular mechanisms of complement evasion: learning from staphylococci and meningococci.
  Nat Rev Microbiol, 8, 393-399.  
20108004 H.Tawadrous, T.Maga, J.Sharma, J.Kupferman, R.J.Smith, and M.Schoeneman (2010).
A novel mutation in the complement factor B gene (CFB) and atypical hemolytic uremic syndrome.
  Pediatr Nephrol, 25, 947-951.  
20585457 S.Fu, X.Tong, C.Cai, Y.Zhao, Y.Wu, Y.Li, J.Xu, X.C.Zhang, L.Xu, W.Chen, and Z.Rao (2010).
The structure of tumor endothelial marker 8 (TEM8) extracellular domain and implications for its receptor function for recognizing anthrax toxin.
  PLoS One, 5, e11203.
PDB code: 3n2n
20974933 Z.Chen, L.A.Pelc, and E.Di Cera (2010).
Crystal structure of prethrombin-1.
  Proc Natl Acad Sci U S A, 107, 19278-19283.
PDB code: 3nxp
19473969 A.Bah, C.J.Carrell, Z.Chen, P.S.Gandhi, and E.Di Cera (2009).
Stabilization of the E* form turns thrombin into an anticoagulant.
  J Biol Chem, 284, 20034-20040.
PDB code: 3gic
19574954 B.J.Janssen, L.Gomes, R.I.Koning, D.I.Svergun, A.J.Koster, D.C.Fritzinger, C.W.Vogel, and P.Gros (2009).
Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex.
  EMBO J, 28, 2469-2478.
PDB codes: 3hrz 3hs0
19180666 E.Di Cera (2009).
Serine proteases.
  IUBMB Life, 61, 510-515.  
19136636 E.Torreira, A.Tortajada, T.Montes, S.R.de Córdoba, and O.Llorca (2009).
3D structure of the C3bB complex provides insights into the activation and regulation of the complement alternative pathway convertase.
  Proc Natl Acad Sci U S A, 106, 882-887.  
19586901 P.S.Gandhi, M.J.Page, Z.Chen, L.Bush-Pelc, and E.Di Cera (2009).
Mechanism of the anticoagulant activity of thrombin mutant W215A/E217A.
  J Biol Chem, 284, 24098-24105.
PDB codes: 3hk3 3hk6 3hki 3hkj
19503103 S.H.Rooijakkers, J.Wu, M.Ruyken, R.van Domselaar, K.L.Planken, A.Tzekou, D.Ricklin, J.D.Lambris, B.J.Janssen, J.A.van Strijp, and P.Gros (2009).
Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor.
  Nat Immunol, 10, 721-727.
PDB code: 2win
19237749 V.Krishnan, Y.Xu, K.Macon, J.E.Volanakis, and S.V.Narayana (2009).
The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation.
  Acta Crystallogr D Biol Crystallogr, 65, 266-274.
PDB code: 3erb
19846563 W.Niu, Z.Chen, L.A.Bush-Pelc, A.Bah, P.S.Gandhi, and E.Di Cera (2009).
Mutant N143P reveals how Na+ activates thrombin.
  J Biol Chem, 284, 36175-36185.
PDB codes: 3jz1 3jz2
18064050 P.Gros, F.J.Milder, and B.J.Janssen (2008).
Complement driven by conformational changes.
  Nat Rev Immunol, 8, 48-58.  
17684013 B.J.Janssen, E.F.Halff, J.D.Lambris, and P.Gros (2007).
Structure of compstatin in complex with complement component C3c reveals a new mechanism of complement inhibition.
  J Biol Chem, 282, 29241-29247.
PDB code: 2qki
17182750 E.Goicoechea de Jorge, C.L.Harris, J.Esparza-Gordillo, L.Carreras, E.A.Arranz, C.A.Garrido, M.López-Trascasa, P.Sánchez-Corral, B.P.Morgan, and S.Rodríguez de Córdoba (2007).
Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome.
  Proc Natl Acad Sci U S A, 104, 240-245.  
17310251 F.J.Milder, L.Gomes, A.Schouten, B.J.Janssen, E.G.Huizinga, R.A.Romijn, W.Hemrika, A.Roos, M.R.Daha, and P.Gros (2007).
Factor B structure provides insights into activation of the central protease of the complement system.
  Nat Struct Mol Biol, 14, 224-228.
PDB code: 2ok5
17921140 G.T.Le, G.Abbenante, and D.P.Fairlie (2007).
Profiling the enzymatic properties and inhibition of human complement factor B.
  J Biol Chem, 282, 34809-34816.  
17234210 V.Krishnan, Y.Xu, K.Macon, J.E.Volanakis, and S.V.Narayana (2007).
The crystal structure of C2a, the catalytic fragment of classical pathway C3 and C5 convertase of human complement.
  J Mol Biol, 367, 224-233.
PDB codes: 2odp 2odq
17027507 F.J.Milder, H.C.Raaijmakers, M.D.Vandeputte, A.Schouten, E.G.Huizinga, R.A.Romijn, W.Hemrika, A.Roos, M.R.Daha, and P.Gros (2006).
Structure of complement component C2A: implications for convertase formation and substrate binding.
  Structure, 14, 1587-1597.
PDB codes: 2i6q 2i6s
17098186 T.A.Springer (2006).
Complement and the multifaceted functions of VWA and integrin I domains.
  Structure, 14, 1611-1616.  
16086019 S.H.Rooijakkers, M.Ruyken, A.Roos, M.R.Daha, J.S.Presanis, R.B.Sim, W.J.van Wamel, K.P.van Kessel, and J.A.van Strijp (2005).
Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases.
  Nat Immunol, 6, 920-927.  
15342015 G.Hauptmann, and S.Bahram (2004).
Genetics of the central MHC.
  Curr Opin Immunol, 16, 668-672.  
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 code is shown on the right.

 

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