3AYK

CATALYTIC FRAGMENT OF HUMAN FIBROBLAST COLLAGENASE COMPLEXED WITH CGS-27023A, NMR, MINIMIZED AVERAGE STRUCTURE


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 
  • Selection Criteria: LOWEST ENERGY, LOWEST VIOLATIONS, CONSISTENT FOLD 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

NMR solution structure of the catalytic fragment of human fibroblast collagenase complexed with a sulfonamide derivative of a hydroxamic acid compound.

Moy, F.J.Chanda, P.K.Chen, J.M.Cosmi, S.Edris, W.Skotnicki, J.S.Wilhelm, J.Powers, R.

(1999) Biochemistry 38: 7085-7096

  • DOI: https://doi.org/10.1021/bi982576v
  • Primary Citation of Related Structures:  
    3AYK, 4AYK

  • PubMed Abstract: 

    The solution structure of the catalytic fragment of human fibroblast collagenase (MMP-1) complexed with a sulfonamide derivative of a hydroxamic acid compound (CGS-27023A) has been determined using two-dimensional and three-dimensional heteronuclear NMR spectroscopy. The solution structure of the complex was calculated by means of hybrid distance geometry-simulated annealing using a combination of experimental NMR restraints obtained from the previous refinement of the inhibitor-free MMP-1 (1) and recent restraints for the MMP-1:CGS-27023A complex. The hydroxamic acid moiety of CGS-27023A was found to chelate to the "right" of the catalytic zinc where the p-methoxyphenyl sits in the S1' active-site pocket, the isopropyl group is in contact with H83 and N80, and the pyridine ring is solvent exposed. The sulfonyl oxygens are in hydrogen-bonding distance to the backbone NHs of L81 and A82. This is similar to the conformation determined by NMR of the inhibitor bound to stromelysin (2, 3). A total of 48 distance restraints were observed between MMP-1 and CGS-27023A from 3D 13C-edited/12C-filtered NOESY and 3D 15N-edited NOESY experiments. An additional 18 intramolecular restraints were observed for CGS-27023A from a 2D 12C-filtered NOESY experiment. A minimal set of NMR experiments in combination with the free MMP-1 assignments were used to assign the MMP-1 (1)H, 13C, and 15N resonances in the MMP-1:CGS-27023A complex. The assignments of CGS-27023A in the complex were obtained from 2D 12C-filtered NOESY and 2D 12C-filtered TOCSY experiments.


  • Organizational Affiliation

    Department of Structural Biology, Wyeth-Ayerst Research, Pearl River, New York 10965, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN (COLLAGENASE)169Homo sapiensMutation(s): 0 
EC: 3.4.24.7
UniProt & NIH Common Fund Data Resources
Find proteins for P03956 (Homo sapiens)
Explore P03956 
Go to UniProtKB:  P03956
PHAROS:  P03956
GTEx:  ENSG00000196611 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03956
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CGS
Query on CGS

Download Ideal Coordinates CCD File 
E [auth A]N-HYDROXY-2(R)-[[(4-METHOXYPHENYL)SULFONYL](3-PICOLYL)AMINO]-3-METHYLBUTANAMIDE HYDROCHLORIDE
C18 H23 N3 O5 S
BSIZUMJRKYHEBR-QGZVFWFLSA-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
CGS BindingDB:  3AYK Ki: 33 (nM) from 1 assay(s)
IC50: min: 2.5, max: 96 (nM) from 10 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 
  • Selection Criteria: LOWEST ENERGY, LOWEST VIOLATIONS, CONSISTENT FOLD 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1999-06-07
    Type: Initial release
  • Version 1.1: 2007-10-16
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2019-10-30
    Changes: Data collection, Database references, Derived calculations
  • Version 1.4: 2023-12-27
    Changes: Data collection, Database references, Derived calculations