1UMS

STROMELYSIN-1 CATALYTIC DOMAIN WITH HYDROPHOBIC INHIBITOR BOUND, PH 7.0, 32OC, 20 MM CACL2, 15% ACETONITRILE; NMR ENSEMBLE OF 20 STRUCTURES

Summary for 1UMS

• Entry DOI: 10.2210/pdb1ums/pdb
• Related PRD ID: PRD_000247
• Descriptor: STROMELYSIN-1, ZINC ION, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: zinc hydrolase, metzincin, matrix metalloproteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 20133.10

Authors

Van Doren, S.R.,Kurochkin, A.V.,Hu, W.,Zuiderweg, E.R.P. (deposition date: 1995-10-31, release date: 1996-03-08, Last modification date: 2024-05-01)

Primary citation

Van Doren, S.R.,Kurochkin, A.V.,Hu, W.,Ye, Q.Z.,Johnson, L.L.,Hupe, D.J.,Zuiderweg, E.R.
Solution structure of the catalytic domain of human stromelysin complexed with a hydrophobic inhibitor.
Protein Sci., 4:2487-2498, 1995

PubMed Abstract: Stromelysin, a representative matrix metalloproteinase and target of drug development efforts, plays a prominent role in the pathological proteolysis associated with arthritis and secondarily in that of cancer metastasis and invasion. To provide a structural template to aid the development of therapeutic inhibitors, we have determined a medium-resolution structure of a 20-kDa complex of human stromelysin's catalytic domain with a hydrophobic peptidic inhibitor using multinuclear, multidimensional NMR spectroscopy. This domain of this zinc hydrolase contains a mixed beta-sheet comprising one antiparallel strand and four parallel strands, three helices, and a methionine-containing turn near the catalytic center. The ensemble of 20 structures was calculated using, on average, 8 interresidue NOE restraints per residue for the 166-residue protein fragment complexed with a 4-residue substrate analogue. The mean RMS deviation (RMSD) to the average structure for backbone heavy atoms is 0.91 A and for all heavy atoms is 1.42 A. The structure has good stereochemical properties, including its backbone torsion angles. The beta-sheet and alpha-helices of the catalytic domains of human stromelysin (NMR model) and human fibroblast collagenase (X-ray crystallographic model of Lovejoy B et al., 1994b, Biochemistry 33:8207-8217) superimpose well, having a pairwise RMSD for backbone heavy atoms of 2.28 A when three loop segments are disregarded. The hydroxamate-substituted inhibitor binds across the hydrophobic active site of stromelysin in an extended conformation. The first hydrophobic side chain is deeply buried in the principal S'1 subsite, the second hydrophobic side chain is located on the opposite side of the inhibitor backbone in the hydrophobic S'2 surface subsite, and a third hydrophobic side chain (P'3) lies at the surface.

PubMed: 8580839

Experimental method

SOLUTION NMR