Crystal structure of phosphatidylglycerophosphatase (PGPase), a putative membrane-bound lipid phosphatase, reveals a novel binuclear metal binding site and two "proton wires"

Desigan Kumaran, Jeffrey B. Bonanno, Stephen K. Burley, Subramanyam Swaminathan

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Phosphatidylglycerophosphatase (PGPase), an enzyme involved in lipid metabolism, catalyzes formation of phosphatidylglycerol from phosphatidylglycerophosphate. Phosphatidylglycerol is a multifunctional phospholipid, found in the biological membranes of many organisms. Here, we report the crystal structure of Listeria monocytogenes PGPase at 1.8 Å resolution. PGPase, an allhelical molecule, forms a homotetramer. Each protomer contains an independent active site with two metal ions, Ca2+ and Mg2+, forming a heterobinuclear center located in a hydrophilic cavity near the surface of the molecule. The binuclear center, conserved ligands, metal-bound water molecules, and an Asp-His dyad form the active site. The catalytic mechanism of this enzyme is likely to proceed via binuclear metal activated nucleophilic water. The binuclear metal-binding active-site environment of this structure should provide insights into substrate binding and metal-dependent catalysis. A long channel with inter-linked linear water chains, termed "proton wires," is observed at the tetramer interface. Comparison of similar water chain structures in photosynthetic reaction centers (RCs), Cytochrome f, gramicidin, and bacteriorhodopsin, suggests that PGPase may conduct protons via proton wires.

Original languageEnglish (US)
Pages (from-to)851-862
Number of pages12
JournalProteins: Structure, Function and Genetics
Volume64
Issue number4
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

Fingerprint

phosphatidylglycerophosphatase
Membrane Lipids
Phosphoric Monoester Hydrolases
Protons
Crystal structure
Metals
Binding Sites
Wire
Membranes
Lipids
Phosphatidylglycerols
Water
Catalytic Domain
Molecules
Cytochromes f
Photosynthetic Reaction Center Complex Proteins
Listeria
Biological membranes
Bacteriorhodopsins
Gramicidin

Keywords

  • Binuclear metal site
  • Lipid metabolism
  • PGPase
  • Phosphatase
  • Proton wires

ASJC Scopus subject areas

  • Genetics
  • Structural Biology
  • Biochemistry

Cite this

Crystal structure of phosphatidylglycerophosphatase (PGPase), a putative membrane-bound lipid phosphatase, reveals a novel binuclear metal binding site and two "proton wires". / Kumaran, Desigan; Bonanno, Jeffrey B.; Burley, Stephen K.; Swaminathan, Subramanyam.

In: Proteins: Structure, Function and Genetics, Vol. 64, No. 4, 01.09.2006, p. 851-862.

Research output: Contribution to journalArticle

@article{f6017901b00a481b8ae89dd7eb95ce7f,
title = "Crystal structure of phosphatidylglycerophosphatase (PGPase), a putative membrane-bound lipid phosphatase, reveals a novel binuclear metal binding site and two {"}proton wires{"}",
abstract = "Phosphatidylglycerophosphatase (PGPase), an enzyme involved in lipid metabolism, catalyzes formation of phosphatidylglycerol from phosphatidylglycerophosphate. Phosphatidylglycerol is a multifunctional phospholipid, found in the biological membranes of many organisms. Here, we report the crystal structure of Listeria monocytogenes PGPase at 1.8 {\AA} resolution. PGPase, an allhelical molecule, forms a homotetramer. Each protomer contains an independent active site with two metal ions, Ca2+ and Mg2+, forming a heterobinuclear center located in a hydrophilic cavity near the surface of the molecule. The binuclear center, conserved ligands, metal-bound water molecules, and an Asp-His dyad form the active site. The catalytic mechanism of this enzyme is likely to proceed via binuclear metal activated nucleophilic water. The binuclear metal-binding active-site environment of this structure should provide insights into substrate binding and metal-dependent catalysis. A long channel with inter-linked linear water chains, termed {"}proton wires,{"} is observed at the tetramer interface. Comparison of similar water chain structures in photosynthetic reaction centers (RCs), Cytochrome f, gramicidin, and bacteriorhodopsin, suggests that PGPase may conduct protons via proton wires.",
keywords = "Binuclear metal site, Lipid metabolism, PGPase, Phosphatase, Proton wires",
author = "Desigan Kumaran and Bonanno, {Jeffrey B.} and Burley, {Stephen K.} and Subramanyam Swaminathan",
year = "2006",
month = "9",
day = "1",
doi = "10.1002/prot.21039",
language = "English (US)",
volume = "64",
pages = "851--862",
journal = "Proteins: Structure, Function and Bioinformatics",
issn = "0887-3585",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Crystal structure of phosphatidylglycerophosphatase (PGPase), a putative membrane-bound lipid phosphatase, reveals a novel binuclear metal binding site and two "proton wires"

AU - Kumaran, Desigan

AU - Bonanno, Jeffrey B.

AU - Burley, Stephen K.

AU - Swaminathan, Subramanyam

PY - 2006/9/1

Y1 - 2006/9/1

N2 - Phosphatidylglycerophosphatase (PGPase), an enzyme involved in lipid metabolism, catalyzes formation of phosphatidylglycerol from phosphatidylglycerophosphate. Phosphatidylglycerol is a multifunctional phospholipid, found in the biological membranes of many organisms. Here, we report the crystal structure of Listeria monocytogenes PGPase at 1.8 Å resolution. PGPase, an allhelical molecule, forms a homotetramer. Each protomer contains an independent active site with two metal ions, Ca2+ and Mg2+, forming a heterobinuclear center located in a hydrophilic cavity near the surface of the molecule. The binuclear center, conserved ligands, metal-bound water molecules, and an Asp-His dyad form the active site. The catalytic mechanism of this enzyme is likely to proceed via binuclear metal activated nucleophilic water. The binuclear metal-binding active-site environment of this structure should provide insights into substrate binding and metal-dependent catalysis. A long channel with inter-linked linear water chains, termed "proton wires," is observed at the tetramer interface. Comparison of similar water chain structures in photosynthetic reaction centers (RCs), Cytochrome f, gramicidin, and bacteriorhodopsin, suggests that PGPase may conduct protons via proton wires.

AB - Phosphatidylglycerophosphatase (PGPase), an enzyme involved in lipid metabolism, catalyzes formation of phosphatidylglycerol from phosphatidylglycerophosphate. Phosphatidylglycerol is a multifunctional phospholipid, found in the biological membranes of many organisms. Here, we report the crystal structure of Listeria monocytogenes PGPase at 1.8 Å resolution. PGPase, an allhelical molecule, forms a homotetramer. Each protomer contains an independent active site with two metal ions, Ca2+ and Mg2+, forming a heterobinuclear center located in a hydrophilic cavity near the surface of the molecule. The binuclear center, conserved ligands, metal-bound water molecules, and an Asp-His dyad form the active site. The catalytic mechanism of this enzyme is likely to proceed via binuclear metal activated nucleophilic water. The binuclear metal-binding active-site environment of this structure should provide insights into substrate binding and metal-dependent catalysis. A long channel with inter-linked linear water chains, termed "proton wires," is observed at the tetramer interface. Comparison of similar water chain structures in photosynthetic reaction centers (RCs), Cytochrome f, gramicidin, and bacteriorhodopsin, suggests that PGPase may conduct protons via proton wires.

KW - Binuclear metal site

KW - Lipid metabolism

KW - PGPase

KW - Phosphatase

KW - Proton wires

UR - http://www.scopus.com/inward/record.url?scp=33748442330&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748442330&partnerID=8YFLogxK

U2 - 10.1002/prot.21039

DO - 10.1002/prot.21039

M3 - Article

VL - 64

SP - 851

EP - 862

JO - Proteins: Structure, Function and Bioinformatics

JF - Proteins: Structure, Function and Bioinformatics

SN - 0887-3585

IS - 4

ER -