1PWP	Hydrolase	date	Jul 02, 2003
title	Crystal Structure Of The Anthrax Lethal Factor Complexed With Small Molecule Inhibitor Nsc 12155
authors	T.Y.Wong, R.Schwarzenbacher, R.C.Liddington
compound		source
Molecule: Lethal Factor Chain: A, B Synonym: Lf, Anthrax Lethal Toxin Endopeptidase Component Ec: 3.4.24.83 Engineered: Yes		Organism_scientific: Bacillus Anthracis Organism_common: Bacteria Gene: Lef Expression_system: Bacillus Anthracis Expression_system_common: Bacteria Expression_system_strain: Bh441 Expression_system_vector_type: Plasmid Expression_system_plasmid: Px01
symmetry	Space Group: P 1 21 1	R_factor	0.223
crystal cell	length a length b length c angle alpha angle beta angle gamma 96.700 137.400 98.300 90.00 98.00 90.00
method	X-Ray Diffraction	resolution	2.90 Å
ligand	NSC, ZN	enzyme	Anthrax lethal factor endopeptidase;. Lethal toxin. Hydrolase E.C.3.4.24.83 BRENDA
domain	The pa-binding region is found in both b.anthracis ef and lf. Domain iv contains the catalytic center. It comprises four domains translocating component (pa); domains ii, iii and iv together create a long deep groove that holds the 16-residue n-terminal tail of mapkk before cleavage.
similarity	Belongs to the peptidase m34 family.[ATLF]
subunit	Anthrax toxins are composed of three distinct proteins, a protective antigen (pa), a lethal factor (lf) and an edema factor (ef). None of these is toxic by itself. Pa+lf forms the lethal toxin (letx); pa+ef forms the edema toxin (edtx).
catalytic activ.	The only known protein substrates are mitogen-activated protein (map) kinase kinases. Preferred amino acids around the cleavage site can be denoted bbbbxhx-|-h, in which b denotes arg or lys, h denotes a hydrophobic amino acid, and x is any amino acid.
induction	Positively transcriptionally regulated by atxa, which, in turn, is induced by bicarbonate and high temperatures (37 degrees celsius).
subcellular loc.	Secreted protein.
genes	BXA0172, GBAA, lef (B. anthracis)
function	Lf is not toxic by itself. It is a protease that cleaves the n-terminal of most dual specificity mitogen-activated protein kinase kinases (mapkks or map2ks) (except for map2k5). One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. Cleavage invariably occurs within the n-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes. There may be other cytosolic targets of lf involved in cytotoxicity. Lf is the lethal factor that, when associated with pa, causes death. The proteasome may mediate a toxic process initiated by lf in the cell cytosol involving degradation of unidentified molecules that are essential for macrophage homeostasis. This is an early step in letx intoxication, but it is downstream of the cleavage by lf of mek1 or other putative substrates.
Gene Ontology	Chain Function Process Component A, B peptidase activity metallopeptidase activity zinc ion binding hydrolase activity metal ion binding proteolysis pathogenesis extracellular region
Primary reference	Identification of small molecule inhibitors of anthrax lethal factor., Panchal RG, Hermone AR, Nguyen TL, Wong TY, Schwarzenbacher R, Schmidt J, Lane D, McGrath C, Turk BE, Burnett J, Aman MJ, Little S, Sausville EA, Zaharevitz DW, Cantley LC, Liddington RC, Gussio R, Bavari S, Nat Struct Mol Biol 2004 Jan;11(1):67-72. Epub 2003 Dec 29. PMID:14718925

Data retrieval

Asymmetric unit, PDB entry: [header only] [complete with coordinates] (276 Kb) [Save to disk] Biological Unit Coordinates (1pwp.pdb1.gz) 124 Kb Biological Unit Coordinates (1pwp.pdb2.gz) 126 Kb CSU: Contacts of Structural Units for 1PWP Likely Quarternary Molecular Structure file(s) for 1PWP Structure Factors (411 Kb) Retrieve 1PWP in mmCIF format [Save to disk]

View 1PWP in 3D

On Jmol, a nice Rasmol like molecule viewer. This is good for easiest viewing of basic structure. On FirstGlance, an excellent tool for a guided tour on the structure components, by E. Martz. On AstexViewer, from MSD-EBI (viewer documentation). On RasMol (Install RasMol freeware) Here's help on how to use RasMol.

Visual 3D analysis of 1PWP

Protein Explorer, Easier to use and more powerful than RasMol. (Win and Mac only) Noncovalent Bond Finder displays the closest contacts to ligand or interface, reports distances, walks over water bridges. STING, shows the sequence and maps the locations of sequence residues or residue ranges onto the 3D structure. GRASS (Graphical Representation and Analysis of Structure Server) Cartoon representation from PDB Cartoon Ramachandran plot from PDBSum

Structure-derived information

Electron Density related parameters from EDS Electron Density Server, at Upsala Dipole moment, from Dipole Server at Weizmann Institute Crystal Contacts, from CryCo at Weizmann Institute 3D motif for 1PWP, from MSDmotif at EBI Classification of representative domains in scop (Structural Classification of Proteins)     - Domain d1pwpa3, region A:264-550 [Jmol] [rasmolscript] [script source]     - Domain d1pwpa1, region A:30-263 [Jmol] [rasmolscript] [script source]     - Domain d1pwpa2, region A:551-776 [Jmol] [rasmolscript] [script source]     - Domain d1pwpb3, region B:264-550 [Jmol] [rasmolscript] [script source]     - Domain d1pwpb1, region B:31-263 [Jmol] [rasmolscript] [script source]     - Domain d1pwpb2, region B:551-776 [Jmol] [rasmolscript] [script source] Fold representative 1pwp from FSSP and Dali (Families of Structurally Similar Proteins) Class (fold), Architecture (subfold), Topology, Homologous superfamily from CATH Summaries and structural analyses of PDB data files from PDBSum Identification of Protein Pockets & Cavities at CASTp

Sequence-derived information

View one-letter amino acid or nucleotide sequence for each chain: [1pwp_A] [1pwp_B]

Other resources with information on 1PWP

InterPro: IPR003541 , IPR006025 MMDB (Entrez's Structure Database)

Movements, Movies and Images

Images from IMB Jena Image Library of Biological Macromolecules.

You may enter another PDB ID code

Go [Back], to the [PDB Lite page], to the [OCA Search page] or to the [PDB Home page]

---

OCA© by Jaime Prilusky, 1996-2006
Bioinformatics and Biological Computing
Weizmann Institute of Science

---