DB code: S00361

RLCP classification	1.12.30000.24 : Hydrolysis
CATH domain	3.40.50.1110 : Rossmann fold	Catalytic domain
E.C.	3.1.1.47
CSA	1bwp
M-CSA	1bwp
MACiE	M0094

CATH domain	Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	RefSeq
Q29460	Platelet-activating factor acetylhydrolase IB subunit gamma	EC 3.1.1.47 PAF acetylhydrolase 29 kDa subunit PAF-AH 29 kDa subunit PAF-AH subunit gamma PAFAH subunit gamma	NP_777090.1 (Protein) NM_174665.2 (DNA/RNA sequence)

KEGG enzyme name
1-alkyl-2-acetylglycerophosphocholine esterase 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine acetylhydrolase alkylacetyl-GPC:acetylhydrolase

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
Q29460	PA1B3_BOVIN	1-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H(2)O = 1-alkyl-sn-glycero-3-phosphocholine + acetate.	Cytosolic PAF-AH IB is formed of three subunits of 45 kDa (alpha), 30 kDa (beta) and 29 kDa (gamma). The catalytic activity of the enzyme resides in the beta and gamma subunits, whereas the alpha subunit has regulatory activity. Trimer formation is not essential for the catalytic activity.	Cytoplasm.

KEGG Pathways
Map code	Pathways	E.C.
MAP00565	Ether lipid metabolism

Compound table
	Substrates		Products		Intermediates
KEGG-id	C04598	C00001	C04317	C00033
E.C.
Compound	1-Alkyl-2-acetyl-sn-glycero-3-phosphocholine	H2O	1-Alkyl-sn-glycerol-3-phosphocholine	Acetate
Type	amine group,carbohydrate,lipid,phosphate group/phosphate ion	H2O	amine group,carbohydrate,lipid,phosphate group/phosphate ion	carboxyl group
ChEBI		15377 15377		15366 15366
PubChem		22247451 962 22247451 962		176 21980959 176 21980959

1bwpA	Unbound		Unbound	Unbound
1bwqA	Unbound		Unbound	Unbound
1bwrA	Unbound		Unbound	Unbound
1es9A	Unbound		Unbound	Unbound
1wabA	Unbound		Unbound	Bound:ACT

Reference for Active-site residues
resource	references	E.C.
Swiss-prot;Q29460

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

1bwpA	SER 47;ASN 104;ASP 192;HIS 195			SER 47;GLY 74
1bwqA	SER 47;ASN 104;ASP 192;HIS 195			SER 47;GLY 74
1bwrA	SER 47;ASN 104;ASP 192;HIS 195			SER 47;GLY 74
1es9A	SER 47;ASN 104;ASP 192;HIS 195			SER 47;GLY 74
1wabA	SER 47;ASN 104;ASP 192;HIS 195			SER 47;GLY 74

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[1]	p.90-92.
[2]	p.698-699
[4]	p.869-870

References
[1]
Resource
Comments	X-ray crystallography (1.7 Angstroms)
Medline ID
PubMed ID	8985254
Journal	Nature
Year	1997
Volume	385
Pages	89-93
Authors	Ho YS, Swenson L, Derewenda U, Serre L, Wei Y, Dauter Z, Hattori M, Adachi T, Aoki J, Arai H, Inoue K, Derewenda ZS
Title	Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer.
Related PDB	1wab
Related UniProtKB
[2]
Resource
Comments	X-ray crystallography (1.7 Angstroms)
Medline ID
PubMed ID	10469831
Journal	Protein Eng
Year	1999
Volume	12
Pages	693-700
Authors	Ho YS, Sheffield PJ, Masuyama J, Arai H, Li J, Aoki J, Inoue K, Derewenda U, Derewenda ZS
Title	Probing the substrate specificity of the intracellular brain platelet-activating factor acetylhydrolase.
Related PDB	1bwp 1bwq 1bwr
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID	11080681
Journal	Biochim Biophys Acta
Year	2000
Volume	1488
Pages	102-23
Authors	Tjoelker LW, Stafforini DM
Title	Platelet-activating factor acetylhydrolases in health and disease.
Related PDB
Related UniProtKB
[4]
Resource
Comments	functional consequences of the dimerization
Medline ID
PubMed ID	11239086
Journal	Protein Eng
Year	2000
Volume	13
Pages	865-71
Authors	McMullen TW, Li J, Sheffield PJ, Aoki J, Martin TW, Arai H, Inoue K, Derewenda ZS
Title	The functional implications of the dimerization of the catalytic subunits of the mammalian brain platelet-activating factor acetylhydrolase (Ib).
Related PDB	1es9
Related UniProtKB
[5]
Resource
Comments	X-ray crystallography (2.1 Angstroms)
Medline ID
PubMed ID	11522926
Journal	Protein Eng
Year	2001
Volume	14
Pages	513-9
Authors	Sheffield PJ, McMullen TW, Li J, Ho YS, Garrard SM, Derewenda U, Derewenda ZS
Title	Preparation and crystal structure of the recombinant alpha(1)/alpha(2) catalytic heterodimer of bovine brain platelet-activating factor acetylhydrolase Ib.
Related PDB
Related UniProtKB

Comments
The paper [1] on the crystal structure of this enzyme reported that it has a trypsin-like catalytic triad of Ser47, His195 and Asp 192, as well as an oxyanion hole. Moreover, Ser47 has been identified as the putative nucleohile, whereas the oxyanion hole seems to be composed of mainchain amide groups of Ser47 and Gly74 along with sidechain amide of Asn104, according to this paper [1]. The paper [4] suggested that this enzyme has got another unique feature in the active site. Arg29 and Arg22 in one chain contribute to the catalytic site of the other monomer across the dimer interface. Thus, the dimerization is essential for both stability and catalytic activity of this enzyme [4].

Comments

The paper [1] on the crystal structure of this enzyme reported that it has a trypsin-like catalytic triad of Ser47, His195 and Asp 192, as well as an oxyanion hole. Moreover, Ser47 has been identified as the putative nucleohile, whereas the oxyanion hole seems to be composed of mainchain amide groups of Ser47 and Gly74 along with sidechain amide of Asn104, according to this paper [1].
The paper [4] suggested that this enzyme has got another unique feature in the active site. Arg29 and Arg22 in one chain contribute to the catalytic site of the other monomer across the dimer interface. Thus, the dimerization is essential for both stability and catalytic activity of this enzyme [4].

Created	Updated
2002-07-04	2010-11-30