title: The helping hand of collagenase-3 (MMP-13): 2.7 A crystal structure of its C-terminal haemopexin-like domain.
abstract: Collagenase-3 (MMP-13) is a matrix metalloproteinase involved in human breast cancer pathology and in arthritic processes. The crystal structure of its C-terminal haemopexin-like domain has been solved by molecular replacement and refined to an R-value of 0.195 using data to 2.7 A resolution. This structure reveals a disk-like shape. The chain is folded into a beta-propeller structure of pseudo 4-fold symmetry, with the four propeller blades arranged around a funnel-like tunnel. This central tunnel tube harbours four ions assigned as two calcium and two chloride ions. The C-terminal domain of collagenase-3 has a similar structure to the equivalent domain of gelatinase A and fibroblast collagenase 1; however, its detailed structure and surface charge pattern has a somewhat greater similarity to the latter, in agreement with the subgrouping of MMP-13 with the collagenase subfamily of MMPs. It is proposed that several small structural differences may act together to confer the characteristic binding and cleavage specificities of collagenases for triple-helical substrates, probably in co-operation with a fitting interdomain linker.
authors.affiliation: Max-Planck-Institut für Biochemie, Abteilung für Strukturforschung, Planegg-Martinsreid, Germany.
authors.forename: F X
authors.initials: FX
authors.lastname: Gomis-Rüth
authors.forename: U
authors.initials: U
authors.lastname: Gohlke
authors.forename: M
authors.initials: M
authors.lastname: Betz
authors.forename: V
authors.initials: V
authors.lastname: Knäuper
authors.forename: G
authors.initials: G
authors.lastname: Murphy
authors.forename: C
authors.initials: C
authors.lastname: López-Otín
authors.forename: W
authors.initials: W
authors.lastname: Bode
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D002118:Calcium; D002712:Chlorides; D017364:Collagenases / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006466:Hemopexin / Q000737:chemistry*; D006801:Humans; D053509:Matrix Metalloproteinase 13; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins; D016415:Sequence Alignment
chemical_list: D000596:Amino Acids; D002712:Chlorides; D011994:Recombinant Proteins; D006466:Hemopexin; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D002118:Calcium