PDBsum entry: 1nl2

Hydrolase

PDB id: 1nl2

Contents

Protein chain

146 a.a. *

Ligands

NAG-NAG

NAG

LPS

Metals

_CA ×7

_CL ×3

Waters ×60

* Residue conservation analysis

PDB id:

1nl2

Name:

Hydrolase

Title:

Bovine prothrombin fragment 1 in complex with calcium and lysophosphotidylserine

Structure:

Prothrombin. Chain: a. Fragment: fragment 1 (residues 1-156). Ec: 3.4.21.5

Source:

Bos taurus. Cattle. Organism_taxid: 9913

Resolution:

2.30Å R-factor: 0.236 R-free: 0.274

Authors:

M.Huang,G.Huang,B.Furie,B.Seaton,B.C.Furie

Key ref:

M.Huang et al. (2003). Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins. Nat Struct Biol, 10, 751-756. PubMed id: 12923575 DOI: 10.1038/nsb971

Date:

06-Jan-03 Release date: 16-Sep-03

Protein chain

P00735  (THRB_BOVIN) -  Prothrombin

Seq: 625 a.a.

Struc: 146 a.a.*

* PDB and UniProt seqs differ at 10 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.4.21.5 - Thrombin.
• Reaction: Preferential cleavage: Arg-|-Gly; activates fibrinogen to fibrin and releases fibrinopeptide A and B.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (1 term)
• Biochemical function: calcium ion binding (1 term)

DOI no: 10.1038/nsb971

Nat Struct Biol 10:751-756 (2003)

PubMed id: 12923575

Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins.

M.Huang, A.C.Rigby, X.Morelli, M.A.Grant, G.Huang, B.Furie, B.Seaton, B.C.Furie.

ABSTRACT

In a calcium-dependent interaction critical for blood coagulation, vitamin K-dependent blood coagulation proteins bind cell membranes containing phosphatidylserine via gamma-carboxyglutamic acid-rich (Gla) domains. Gla domain-mediated protein-membrane interaction is required for generation of thrombin, the terminal enzyme in the coagulation cascade, on a physiologic time scale. We determined by X-ray crystallography and NMR spectroscopy the lysophosphatidylserine-binding site in the bovine prothrombin Gla domain. The serine head group binds Gla domain-bound calcium ions and Gla residues 17 and 21, fixed elements of the Gla domain fold, predicting the structural basis for phosphatidylserine specificity among Gla domains. Gla domains provide a unique mechanism for protein-phospholipid membrane interaction. Increasingly Gla domains are being identified in proteins unrelated to blood coagulation. Thus, this membrane-binding mechanism may be important in other physiologic processes.

Selected figure(s)

Figure 2.
Figure 2. Bonding network for binding of lysophosphatidylserine with Ca^2+-liganded PT1. (a) The model is rotated 90° around the y-axis relative to the view in Figure 1b. The hydrogen bonds and salt bridges between atoms in lysophosphatidylserine and the PT1 -calcium ion complex are indicated as dashed lines. (b) The electrostatic potential surface of bovine PT1, generated using GRASP45, is shown in the same view as in a. Positive and negative electrostatic potential on the surface, blue and red, respectively. Lysophosphatidylserine is presented as a stick model. Ca^2+ ions are black spheres.

Figure 4.
Figure 4. Model of PT1 interacting with a phospholipid bilayer. PT1 is shown bound to one leaflet of a phospholipid bilayer composed of phosphatidylcholine with a single lysophosphatidylserine molecule (shown as a stick model). The head group of the lysophosphatidylserine is bound to PT1 as in our crystal structure but the acyl chain of the lysophosphatidylserine is elongated and inserted into the lipid bilayer. The residues of the Gla domain 'hydrophobic patch' of Ca^2+-liganded PT1 are inserted into the interstitial region of the lipid bilayer. PT1 is shown in a space-filling model with residues of the -loop in yellow, the side chain nitrogens of Lys3, Arg10 and Arg16 in blue and Ca^2+ ions in black. Lysophosphatidylserine: carbon, teal; oxygen, red; nitrogen, blue; phosphorous, green.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2003, 10, 751-756) copyright 2003.

Figures were selected by an automated process.