小分子对MMPs活性形式的外源调节器
Ish Kumar1, Melissa Silva1, Dinesh A Choudhary1
1Department of Chemistry, Biochemistry & Physics, Fairleigh Dickinson University, 1000 River Rd, Teaneck, NJ, 07666, USA.
Biochimie
|November 9, 2023
概括
研究人员确定了三个抑制剂 (I1,I2,I3) 和一个激活剂 (L) 活性矩阵金属蛋白酶-1 (MMP-1). 这些调节器有助于恢复MMP-1活动的平衡,这对于治疗相关病理状况至关重要.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
背景情况:
- 矩阵金属蛋白酶 (MMP) 是依赖和的内酶,对组织重塑至关重要.
- MMP活性受到产域和内源性抑制剂 (如金属蛋白酶组织抑制剂 (TIMPs)) 的严格调节.
- 调节不良的MMP恒温与各种病理状况有关.
研究的目的:
- 识别和描述人类活体原酶MMP-1的新型调节剂.
- 研究可以恢复MMP-1活动平衡的化合物.
主要方法:
- 三种新型抑制剂 (I1,I2,I3) 和一种激活剂 (L) 的合成和测试.
- 使用基于光的方法进行酶活性测定.
- 有约束力的研究来确认相互作用.
主要成果:
- 成功鉴定了三种有效的抑制剂 (I1,I2,I3) 和一个外源激活剂 (L) 对活性MMP-1.
- 证明了这些调节剂在改变MMP-1活性方面的有效性.
- 通过基于光的结合试验证实了相互作用.
结论:
- 已识别的抑制剂和激活剂为涉及MMP-1失调的疾病提供了潜在的治疗策略.
- 这些调节器为进一步研究MMP-1功能和抑制提供了工具.
- 恢复MMP-1稳态是一种可行的治疗方法.
相关概念视频
Role of Matrix Metalloproteases in Degradation of ECM
2.4K
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.4K
Microtubule Associated Proteins (MAPs)
4.4K
Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
4.4K
Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action
1.9K
Nondepolarizing neuromuscular blockers induce paralysis by competitively blocking nicotinic acetylcholine receptors at the muscle end plate. Examples include pancuronium, mivacurium, vecuronium, and rocuronium. These quaternary ammonium derivatives are administered intravenously, are poorly absorbed, and are excreted via the kidneys.
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
1.9K
Calmodulin-dependent Signaling
5.2K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.2K
The Extracellular Matrix
82.7K
Overview
82.7K
Antihypertensive Drugs: Vasodilators
540
Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...
540


