Warning: mysql_result() [function.mysql-result]: Unable to jump to row 0 on MySQL result index 5 in /net/isilon4/research/thornton/www/databases/html/CSA_NEW/SearchResults.php on line 83
Catalytic Site Atlas Search Results
spacer
View the latest EBI news stories and important announcements...
more

spacer
Search The CSA
PDB ID
UNIPROT ID
EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1hzf

E.C. nameclassical-complement-pathway C3/C5 convertase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 3.4.21.43
CSA Homologues of 1hzfThere are 19 Homologs
CSA Entries With UniProtID
CSA Entries With EC Number 3.4.21.43
PDBe Entry 1hzf
PDBSum Entry 1hzf
MACiE Entry 1hzf

Literature Report

IntroductionComplement factor C4A is a component of the complement system - the major defence effector in blood plasma. It is involved in propagation of the classical and lectin pathways of the complement system. This is dependent upon the thio-ester mediated transacylation of C4 to a surface nucleophile on the target antigen/pathogen. C4 belongs to a family that share the common feature of having a proteolytically activated intramolecular thio-ester bond capable of forming a covalent adduct. It has two isotypes - C4A and C4B. These differ by four isotype-specific residues which affect their covalent binding properties - C4A allotypes preferentially transacylate onto amino group nucleophiles, whereas C4B allotypes transacylate hydroxyl-bearing target molecules.
MechansimWithin the protein, the four residues -Cys-Gly-Glu-Gln- are highly conserved. This is due to the Cys 991 and Gln 994 being within 2 Angstrom of each other, allowing Cys 991 to nucleophilically attack the carbonyl carbon of Gln 994, forming an intramolecular thio-ester bond. Within the protein, the four residues -Cys-Gly-Glu-Gln- form a fifteen-membered thiolactone ring.
If C4A becomes activated, causing the thioester to be exposed and an amino group is in the immediate surroundings, the amino group will nucleophilically attack the carbonyl carbon of the thio-ester, causing an amide linkage to form and Cys 991 to leave.
Reaction

Catalytic Sites for 1hzf

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
CysA9911010macie:sideChainCys 991 nucleophilically attacks the carbonyl carbon of Gln 994, forming an intramolecular thio-ester bond.
GlnA9941013macie:sideChainGln 994 is nucleophilically attacked by Cys 991, forming an intramolecular thio-ester bond. If C4A becomes activated, causing the thioester to be exposed and an amino group is in the immediate surroundings, the amino group will nucleophilically attack the carbonyl carbon of the thio-ester, causing an amide linkage to form.

Literature References

Notes:
van den Elsen JM
X-ray crystal structure of the C4d fragment of human complement component C4.
J Mol Biol 2002 322 1103-1115
PubMed: 12367531
Law SK
The internal thioester and the covalent binding properties of the complement proteins C3 and C4.
Protein Sci 1997 6 263-274
PubMed: 9041627
spacer
spacer