Solution structure and backbone dynamics of the catalytic domain of matrix metalloproteinase-2 complexed with a hydroxamic acid inhibitor

Feng, Yiqing; Likos, John J.; Zhu, Lianjie; Woodward, Harold; Munie, Grace E.; McDonald, Joseph J.; Stevens, Anna M.; Howard, Carol Pearcy; Crescenzo, Gary A. De; Welsch, Dean J.; Shieh, Huey‐Sheng; Stallings, William C.

doi:10.1016/s0167-4838(02)00307-2

Cited by 92 publications

(92 citation statements)

References 47 publications

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“…The fact that embedded soluble ion-releasing nanoparticles can affect proliferation and migration is not surprising as h-KC migration was previously shown to be affected by the release of iron and zinc ions as specified in the introduction [11], [12], [13], [14], [15], [16]. While KC differentiation, ex vivo, was already described to be induced by topical applications of zinc [16], this parameter has to be studied further in order to supplement the potential effects of our system on the KC behavior.…”

Section: Biological Testingmentioning

confidence: 94%

“…This process necessitates the synthesis of proteases by macrophages. The protease family mainly involved in wound healing is the matrix metallo-proteases (MMP), which is zinc dependent as its active site directly relies on a zinc ion [11], [12], [13]. Neutrophils, for their part, are known to show an enhanced oxidative metabolism under zinc ions influence [14].…”

Section: Introductionmentioning

confidence: 99%

“…Hereby zinc was shown to take a part in the KC differentiation mechanisms [16]. Finally the scar tissues are remodelled by a turn over between degradation of type III collagen by MMPs and type I neocollagenesis, where respectively zinc and iron are imperative [11], [12], [13], [15]. Based on this, it may be concluded that an optimized ion release system for zinc and iron based on nanocomposites would be highly beneficial to aide in wound healing, while the embedded nanoparticles could serve as excellent ion release source because of their high surface-to-volume ratio.…”

Section: Introductionmentioning

confidence: 99%

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Water-based, surfactant-free cytocompatible nanoparticle-microgel-composite biomaterials – rational design by laser synthesis, processing into fiber pads and impact on cell proliferation

et al. 2017

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Abstract:This work highlights the laser-based aqueous synthesis and processing of nanocomposites, composed of zinc or iron nanoparticles embedded in a N-Vinylcaprolactam microgel matrix, with potential applicability as ion releasing fiber pads for wound healing. An in situ laser process for microgel synthesis is developed and optimized for high embedded nanoparticle yields, evaluating influences of laser repetition rate and monomer concentration. The impact of the nanoparticles on polymerization was increased by embedded zinc oxide nanoparticles, and reduced in the presence of iron oxide. Furthermore, TEM images verified that the nanoparticles were homogeneously embedded into the polymer matrix. The nanoparticle-loaded microgels were thermally stable up to 429°C, which ensures that the composites maintain their integrity after heat sterilization and during rapid prototyping by thermal polymer processing. The general suitability of the hydrogels as active biomaterial for wound healing was assessed in toxicity, cell proliferation and migration assays using human dermal fibroblasts and keratinocytes, where cytocompatibility was verified, while the proliferation was affected by the gel alone as well as the embedded nanoparticles. The hydrogels were processed to suit their use as a biomaterial for wound coverages via electrospinning resulting in a centimeter scale fully cytocompatible fiber pad with the nanoparticle-filled microgel capsules supported on the fiber's surface.

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Section: Biological Testingmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Water-based, surfactant-free cytocompatible nanoparticle-microgel-composite biomaterials – rational design by laser synthesis, processing into fiber pads and impact on cell proliferation

et al. 2017

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“…Astacin (1AST) [38], Matrix metalloproteases (1HOV) [39], Predicted metal-dependent hydrolase (1XM5) [40] and gliadin (2NNA) [41] were downloaded from Protein Data Bank. All three of them have complete crystal structures except for gliadin protein.…”

Section: Fold Based Template Identificationmentioning

confidence: 99%

“…All these crystals have ions intact within the active site (1AST-Astacus astacus has bound zinc ion [47]; 1HOV-MMP-2 with bound zinc ion [48]; 1XM5-metal-dependent hydrolase ybeY from E.coli has bound with Nickel. [49] 3.…”

Section: Structural Superimposition Analysismentioning

confidence: 99%

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2017

RJLBPCS

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Introduction: Gliadin intake causes celiac disease in selected population of Homo sapiens. Short motifs in α/β gliadin wheat protein were behind this food related disorder. Materials and Methods: Fold based template selection software GenTHREADER was considered for template selection and Modeller software was used for modelling wheat gliadin. T-Coffee software was used for the sequence alignment. Finally, antigenic region was identified. Results: Through in silico based study, we identified a novel motif 'HNxxH' in α/β gliadin wheat gliadin in C-terminal region which shows striking resemblance with the helical zinc binding motif 'HExxH' of metalloproteases.Interestingly, this short segment of gliadin is reported to be both an antigen and toxin which aligns well with the zinc binding site of the metalloproteases. Sequence analysis reports a spatial arrangement of the first two histidine residues from predicted motif of gliadin very much similar to the arrangement exhibited by the histidine residues in the selected metalloproteases like Astacin, Matrix metalloproteases and Predicted metal-dependent hydrolase. Additionally, glutamic acid, glycine and histidine from 2 nd , 8 th and 11 th position were substituted by asparagine, isoleucine and glutamine, respectively in this domain. Conclusion: A wet lab based analysis could certainly confirm the evolutionary relatedness of both gliadin and metalloproteases from sequential, structural and immunological perspective.

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Von der Natur inspiriertes Wirkstoffdesign: kristallographische Detektion eines selbstgenerierten Inhibitor‐Grundgerüsts

et al. 2019

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Das De‐novo‐Design neuer Wirkstoffmoleküle ist nach wie vor eine anspruchsvolle Aufgabe bei der Suche nach wirksamen und selektiven Modulatoren für therapeutisch relevante Zielproteine. Hier berichten wir über die unerwartete Entdeckung eines peptidischen Liganden 1 durch Röntgenkristallographie, der vom therapeutischen Zielprotein MMP‐13 durch partiellen Selbstabbau generiert wurde, und die anschließende strukturbasierte Optimierung dieses Peptids zu einem hochwirksamen und selektiven β‐Faltblatt‐Peptidmimetikum der endogenen Gewebeinhibitoren von Metalloproteinasen (TIMPs). Der Einbau von nicht‐proteinogenen Aminosäuren in Kombination mit einer Zyklisierungsstrategie erwies sich als entscheidend für das De‐novo‐Design der TIMP‐Peptidmimetika. Das optimierte zyklische Peptid 4 (ZHAWOC7726) ist membrangängig, hat einen IC50‐Wert von 21 nm für MMP‐13 und ein vielversprechendes Selektivitätsprofil bezüglich eines polypharmakologischen Ansatzes mit den Anti‐Krebs‐Zielproteinen MMP‐2 (IC50: 170 nm) und MMP‐9 (IC50: 140 nm).

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Solution structure and backbone dynamics of the catalytic domain of matrix metalloproteinase-2 complexed with a hydroxamic acid inhibitor

Cited by 92 publications

References 47 publications

Water-based, surfactant-free cytocompatible nanoparticle-microgel-composite biomaterials – rational design by laser synthesis, processing into fiber pads and impact on cell proliferation

Water-based, surfactant-free cytocompatible nanoparticle-microgel-composite biomaterials – rational design by laser synthesis, processing into fiber pads and impact on cell proliferation

Untitled

Von der Natur inspiriertes Wirkstoffdesign: kristallographische Detektion eines selbstgenerierten Inhibitor‐Grundgerüsts

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