1JAN

COMPLEX OF PRO-LEU-GLY-HYDROXYLAMINE WITH THE CATALYTIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (PHE79 FORM)

Summary for 1JAN

• Entry DOI: 10.2210/pdb1jan/pdb
• Related PRD ID: PRD_000404
• Descriptor: MATRIX METALLO PROTEINASE-8 (PHE79 FORM), PRO-LEU-GLY-HYDROXYLAMINE INHIBITOR, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: metalloprotease, zinc-endopeptidase, metzincins, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasmic granule: P22894
• Total number of polymer chains: 2
• Total formula weight: 18770.25

Authors

Reinemer, P.,Grams, F.,Huber, R.,Kleine, T.,Schnierer, S.,Pieper, M.,Tschesche, H.,Bode, W. (deposition date: 1996-03-11, release date: 1996-07-11, Last modification date: 2024-06-05)

Primary citation

Reinemer, P.,Grams, F.,Huber, R.,Kleine, T.,Schnierer, S.,Piper, M.,Tschesche, H.,Bode, W.
Structural implications for the role of the N terminus in the 'superactivation' of collagenases. A crystallographic study.
FEBS Lett., 338:227-233, 1994

PubMed Abstract: For the collagenases PMNL-CL and FIB-CL, the presence of the N-terminal Phe79 correlates with an increase in proteolytic activity. We have determined the X-ray crystal structure of the recombinant Phe79-Gly242 catalytic domain of human neutrophil collagenase (PMNL-CL, MMP-8) using the recently solved model of the Met80-Gly242 form for phasing and subsequently refined it to a final crystallographic R-factor of 18.0% at 2.5 A resolution. The PMNL-CL catalytic domain is a spherical molecule with a flat active site cleft separating a smaller C-terminal subdomain from a bigger N-terminal domain, that harbours two zinc ions, namely a 'structural' and a 'catalytic' zinc, and two calcium ions. The N-terminal segment prior to Pro86, which is disordered in the Met80-Gly242 form, packs against a concave hydrophobic surface made by the C-terminal helix. The N-terminal Phe79 ammonium group makes a salt link with the side chain carboxylate group of the strictly conserved Asp232. Stabilization of the catalytic site might be conferred via strong hydrogen bonds made by the adjacent, likewise strictly conserved Asp233 with the characteristic 'Met-turn', which forms the base of the active site residues.

PubMed: 8307185
DOI: 10.1016/0014-5793(94)80370-6

Experimental method

X-RAY DIFFRACTION (2.5 Å)