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EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1zrz

E.C. nameprotein kinase C
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz)
CSA Homologues of 1zrzThere are 1410 Homologs
CSA Entries With UniProtID P41743
CSA Entries With EC Number
PDBe Entry 1zrz
PDBSum Entry 1zrz
MACiE Entry 1zrz

Literature Report

IntroductionAtypical protein kinase C iota (aPKC iota) from Homo sapiens catalyses the phosphorylation of a protein by hydrolysing ATP to ADP. aPKC iota can phosphorylate a number of different proteins, including interleukin receptor-associated kinase. aPKCs play critical roles in signalling pathways that control cell growth, differentiation and survival. Therefore they constitute targets for the development of novel therapeutics against cancer, for aPKC iota, specifically colon cancer and chronic myelogenous leukemia.
Mechansim1. Asp 369 acts as a base by abstracting a proton from the phosphoacceptor, activating it for nucleophilic attack on the gamma phosphorus atom of ATP. 2. Asp 369 is stabilised by a hydrogen bond to its main chain carbonyl from Asn 374. 3. The reaction goes through a pentavalent transition state which is stabilised by Lys 371. 4. The proton picked up by Asp 369 is then probably donated to the leaving group ADP.

Catalytic Sites for 1zrz

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AsnA374383macie:sideChainStabilises Asp 369 by hydrogen bonding to its main chain carboxylate.
AspA369378macie:sideChainActs as a general base, deprotonating the phosphoacceptor, activating it for nucleophilic attack on the gamma phosphate of ATP.
LysA371380macie:sideChainStabilises the transition state by hydrogen bonding to the gamma phosphate group of ATP.

Literature References

Notes:This mechanism is based on homologues of other kinases not mentioned in the paper referenced.
Messerschmidt A
Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif.
J Mol Biol 2005 352 918-931
PubMed: 16125198