1UMS

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


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Submitted: 20 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Solution structure of the catalytic domain of human stromelysin complexed with a hydrophobic inhibitor.

Van Doren, S.R.Kurochkin, A.V.Hu, W.Ye, Q.Z.Johnson, L.L.Hupe, D.J.Zuiderweg, E.R.

(1995) Protein Sci 4: 2487-2498

  • DOI: https://doi.org/10.1002/pro.5560041205
  • Primary Citation of Related Structures:  
    1UMS, 1UMT

  • 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.


  • Organizational Affiliation

    Biophysics Research Division, University of Michigan, Ann Arbor 48109-1055, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
STROMELYSIN-1174Homo sapiensMutation(s): 0 
Gene Names: HUMAN STROMELYSIN-1 CATALYTIC
EC: 3.4.24.17
UniProt & NIH Common Fund Data Resources
Find proteins for P08254 (Homo sapiens)
Explore P08254 
Go to UniProtKB:  P08254
PHAROS:  P08254
GTEx:  ENSG00000149968 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08254
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0DS
Query on 0DS

Download Ideal Coordinates CCD File 
E [auth A]N-{(2R)-2-[2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl}-L-leucyl-L-phenylalaninamide
C23 H36 N4 O5
HLSQLCOADIMQBK-QYZOEREBSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
D [auth A]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
0DS BindingDB:  1UMS Ki: 127 (nM) from 1 assay(s)
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Submitted: 20 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1996-03-08
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2013-02-27
    Changes: Other
  • Version 1.4: 2020-09-23
    Changes: Data collection, Database references, Derived calculations, Other