The C-terminal (haemopexin-like) domain structure of human gelatinase A (MMP2): structural implications for its function.
In common with most other matrix metalloproteinases, gelatinase A has a non-catalytic C-terminal domain that displays sequence homology to haemopexin. Crystals of this domain were used by molecular replacement to solve its molecular structure at 2.6 A resolution, which was refined to an R value of 17.9%. This structure has a disc-like shape, with the chain folded into a beta-propeller structure that has pseudo four-fold symmetry. Although the topology and the side-chain arrangement are very similar to the equivalent domain of fibroblast collagenase, significant differences in surface charge and contouring are observable on 1 side of the gelatinase A disc. This difference might be a factor in allowing the gelatinase A C-terminal domain to bind to natural inhibitor TIMP-2.
Max-Planck-Institut für Biochemie, Abteilung für Strukturforschung, Martinsried bei München, Germany.
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U
Gohlke
F X
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Gomis-Rüth
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T
Crabbe
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G
Murphy
A J
AJ
Docherty
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W
Bode
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D018093:Gelatinases / Q000737:chemistry* / Q000378:metabolism*; D006466:Hemopexin / Q000737:chemistry; D006801:Humans; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry*; D011480:Protease Inhibitors / Q000378:metabolism; D017433:Protein Structure, Secondary; D011506:Proteins / Q000378:metabolism; D017385:Sequence Homology; D013329:Structure-Activity Relationship; D013552:Swine; D019716:Tissue Inhibitor of Metalloproteinase-2
D010446:Peptide Fragments; D011480:Protease Inhibitors; D011506:Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D006466:Hemopexin; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2