2ow2
MMP-9 active site mutant with difluoro butanoic acid inhibitorMMP-9 active site mutant with difluoro butanoic acid inhibitor
Template:ABSTRACT PUBMED 17599356
DiseaseDisease
[MMP9_HUMAN] Defects in MMP9 may be a cause of susceptibility to intervertebral disc disease (IDD) [MIM:603932]; also known as lumbar disk herniation (LDH). IDD is one of the most common musculo-skeletal disorders and the predominant cause of low-back pain and unilateral leg pain.[1] Defects in MMP9 are the cause of metaphyseal anadysplasia type 2 (MANDP2) [MIM:613073]. Metaphyseal anadysplasia consists of an abnormal bone development characterized by severe skeletal changes that, in contrast with the progressive course of most other skeletal dysplasias, resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.
FunctionFunction
[MMP9_HUMAN] May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.[2]
About this StructureAbout this Structure
2ow2 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
See AlsoSee Also
ReferenceReference
- ↑ Tochowicz A, Maskos K, Huber R, Oltenfreiter R, Dive V, Yiotakis A, Zanda M, Pourmotabbed T, Bode W, Goettig P. Crystal structures of MMP-9 complexes with five inhibitors: contribution of the flexible Arg424 side-chain to selectivity. J Mol Biol. 2007 Aug 24;371(4):989-1006. Epub 2007 May 31. PMID:17599356 doi:http://dx.doi.org/10.1016/j.jmb.2007.05.068
- ↑ Hirose Y, Chiba K, Karasugi T, Nakajima M, Kawaguchi Y, Mikami Y, Furuichi T, Mio F, Miyake A, Miyamoto T, Ozaki K, Takahashi A, Mizuta H, Kubo T, Kimura T, Tanaka T, Toyama Y, Ikegawa S. A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation. Am J Hum Genet. 2008 May;82(5):1122-9. Epub 2008 May 1. PMID:18455130 doi:S0002-9297(08)00223-1
- ↑ Tschesche H, Knauper V, Kramer S, Michaelis J, Oberhoff R, Reinke H. Latent collagenase and gelatinase from human neutrophils and their activation. Matrix Suppl. 1992;1:245-55. PMID:1480034