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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1v0y
Original Entry
Title:
Hydrolase
Compound:
Phospholipase d
Mutant:
No
UniProt/Swiss-Prot:
P84147-P84147
EC Class:
3.1.4.4
Other CSA Entries:
Overview of all sites for 1v0y
Homologues of 1v0y
Entries for UniProt/Swiss-Prot: P84147
Entries for EC: 3.1.4.4
Other Databases:
PDB entry: 1v0y
PDBsum entry: 1v0y
UniProt/Swiss-Prot: P84147
IntEnz entry: 3.1.4.4
Literature Report:
Introduction:
Phospholipase D catalyses the hydrolysis of phospholipids (normally phosphatidyl choline) into phosphatidic acid (PA) and the polar head group (normally choline). The PA generated can be converted into second messengers such as diacylglycerol (DAG) and is also suggested to cause changes in lipid bilayer properties. Phospholipase D will additionally catalyse transphosphatidylation reactions in vitro when an alcohol is present as the nucleophilic donor. It has been shown to be part of a superfamily that includes cardiolipin synthases, phosphatidyl serine synthases, poxvirus envelope proteins and several endonucleases.
Mechanism:
The catalysed hydrolysis reaction occurs in two steps. First, nucleophilic attack by His 170 on the substrate phosphate leads to displacement of the alcohol head group (e.g. choline if the substrate is phosphatidyl choline) and formation of a His-phosphatidate intermediate with a covalent P-N bond to His 170 N-epsilon. The departing polar head group is protonated by His 448. In the second step, His 448 deprotonates a water molecule that attacks the His-phosphatidate intermediate to displace His 170 and produce phosphatidate. Asp 473 and Asp 202 interact with and modify the pKa values of His 170 and His 448 respectively.
Sites:

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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
HISA 170 167Sidechain
NucleophileSubstrate
Attacks phosphate of substrate to form a covalent His-Phosphatidate intermediate that is subsequently hydrolysed.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15165852 Current protein Conservation of residue
PubMed ID 15165852 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 9689058 Related protein: UniProt Q46707 Residue is covalently bound to intermediate, based on non-structural data
PubMed ID 15165852 Current protein Residue is covalently bound to intermediate, based on structural data
PubMed ID 9689058 Related protein: UniProt Q46707 Mutagenesis of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ASPA 202 199Sidechain
ElectrostaticResidue
Modifies pKa of His 448.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15165852 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 15165852 Current protein Conservation of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
HISA 448 440Sidechain
Acid/baseWater
Acid/baseSubstrate
Protonates departing alcohol group (eg choline) during formation of the His-Phosphatidate intermediate. Later deprotonates the water molecule that attacks this intermediate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15165852 Current protein Conservation of residue
PubMed ID 15165852 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ASPA 473 465Sidechain
ElectrostaticResidue
Modifies pKa of His 170.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15165852 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 15165852 Current protein Conservation of residue
References:
1
The reaction mechanism of phospholipase D from Streptomyces sp. strain PMF. Snapshots along the reaction pathway reveal a pentacoordinate reaction intermediate and an unexpected final product.
I. Leiros and S. McSweeney and E. Hough
J Mol Biol. 339 (4), 805-20, (2004)
15165852
2
Catalytic mechanism of the phospholipase D superfamily proceeds via a covalent phosphohistidine intermediate
E. B. Gottlin and A. E. Rudolph and Y. Zhao and H. R. Matthews and J. E. Dixon
Proc Natl Acad Sci USA 95 (16) 9202-7, (1998)
9689058
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