3B8Z

High Resolution Crystal Structure of the Catalytic Domain of ADAMTS-5 (Aggrecanase-2)

PDB DOI: https://doi.org/10.2210/pdb3B8Z/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2007-11-02 Released: 2007-12-11
Deposition Author(s): Shieh, H.-S., Williams, J.M., Mathis, K.J., Tortorella, M.D., Tomasselli, A.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.40 Å
R-Value Free: 0.214
R-Value Work: 0.185
R-Value Observed: 0.187

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

High resolution crystal structure of the catalytic domain of ADAMTS-5 (aggrecanase-2).

Shieh, H.S., Mathis, K.J., Williams, J.M., Hills, R.L., Wiese, J.F., Benson, T.E., Kiefer, J.R., Marino, M.H., Carroll, J.N., Leone, J.W., Malfait, A.M., Arner, E.C., Tortorella, M.D., Tomasselli, A.

(2008) J Biol Chem 283: 1501-1507

PubMed: 17991750 Search on PubMed
DOI: https://doi.org/10.1074/jbc.M705879200
Primary Citation of Related Structures:
3B8Z

PubMed Abstract:
Aggrecanase-2 (a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5)), a member of the ADAMTS protein family, is critically involved in arthritic diseases because of its direct role in cleaving the cartilage component aggrecan. The catalytic domain of aggrecanase-2 has been refolded, purified, and crystallized, and its three-dimensional structure determined to 1.4A resolution in the presence of an inhibitor. A high resolution structure of an ADAMTS/aggrecanase protein provides an opportunity for the development of therapeutics to treat osteoarthritis.

Organizational Affiliation

Pfizer Global Research and Development, St. Louis, Missouri 63017.

Macromolecule Content

Total Structure Weight: 49.33 kDa
Atom Count: 3,920
Modelled Residue Count: 434
Deposited Residue Count: 434
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
protein ADAMTS-5	A, B	217	Homo sapiens	Mutation(s): 1 Gene Names: ADAMTS5, ADAMTS11, ADMP2 EC: 3.4.24
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UNA0 (Homo sapiens) Explore Q9UNA0 Go to UniProtKB: Q9UNA0
PHAROS: Q9UNA0 GTEx: ENSG00000154736
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9UNA0
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
294 Query on 294 Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain L [auth B] MOL2 format, chain G [auth A] MOL2 format, chain L [auth B]	G [auth A], L [auth B]	N-hydroxy-4-({4-[4-(trifluoromethyl)phenoxy]phenyl}sulfonyl)tetrahydro-2H-pyran-4-carboxamide C₁₉ H₁₈ F₃ N O₆ S FOSWRYKPHVPIDJ-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain L [auth B] Interactions & Density Focus chain G [auth A] Focus chain L [auth B]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain H [auth B] MOL2 format, chain C [auth A] MOL2 format, chain H [auth B]	C [auth A], H [auth B]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain H [auth B] Interactions & Density Focus chain C [auth A] Focus chain H [auth B]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain I [auth B] SDF format, chain J [auth B] SDF format, chain K [auth B] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain I [auth B] MOL2 format, chain J [auth B] MOL2 format, chain K [auth B]	D [auth A] E [auth A] F [auth A] I [auth B] J [auth B] D [auth A], E [auth A], F [auth A], I [auth B], J [auth B], K [auth B]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain I [auth B] Focus chain J [auth B] Focus chain K [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain I [auth B] Focus chain J [auth B] Focus chain K [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
294	PDBBind: 3B8Z	IC50: 290 (nM) from 1 assay(s)
294	Binding MOAD: 3B8Z	IC50: 290 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.40 Å
R-Value Free: 0.214
R-Value Work: 0.185
R-Value Observed: 0.187
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 53.057	α = 90
b = 44.487	β = 90.07
c = 76.38	γ = 90

Software Package:

Software Name	Purpose
DENZO	data reduction
SCALEPACK	data scaling
AMoRE	phasing
REFMAC	refinement
PDB_EXTRACT	data extraction
ADSC	data collection
HKL-2000	data reduction
HKL-2000	data scaling