Related Experiment Video
Updated: Nov 24, 2025
06:51
Multilevel Microdissection and Functional-Structural Profiling of Human Renal Arterial Branches
Published on: September 5, 2025
363
Exploring the pH-Dependent Structure-Dynamics-Function Relationship of Human Renin
Shuhua Ma1, Jack A Henderson2, Jana Shen2
1Department of Chemistry, Jess and Mildred Fisher College of Science and Mathematics, Towson University, Towson, Maryland 21252, United States.
Journal of Chemical Information and Modeling
|December 28, 2020
Summary
Renin
Area of Science:
- Biochemistry
- Structural Biology
- Computational Chemistry
Background:
- Renin, an aspartyl protease, is a key drug target for hypertension.
- Its pH-dependent structure-function relationship is poorly understood.
- Aspartyl proteases share common structural features like the flap.
Purpose of the Study:
- To investigate the acid/base roles of renin's catalytic dyad.
- To analyze the conformational dynamics of renin's flap.
- To understand the pH-dependent structure-function relationship of renin.
Main Methods:
- Continuous constant pH molecular dynamics (CpHMD) simulations.
- Calculation of pKa values for catalytic residues.
- Analysis of flap conformational states.
Main Results:
- Catalytic Asp38 acts as a general base, Asp226 as a general acid.
- Hydrogen bonds determine the catalytic dyad's pKa order.
- Renin's flap remains predominantly open, with occasional Tyr-inhibited states above pH 5.
Conclusions:
- Findings support substrate-induced pKa shifts for renin's neutral pH optimum.
- Provides insights into pH-dependent dynamics of aspartyl proteases.
- Establishes a foundation for understanding related enzymes in disease.
Related Concept Videos
01:33Hormonal Regulation
35.1K
The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.
35.1K
01:25Antihypertensive Drugs: Direct Renin Inhibitors
1.0K
The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
1.0K
01:29Physiology of the Genitourinary System I: Renal Blood Flow and Glomerular Filtration
358
The kidneys are vital organs responsible for regulating blood filtration, waste excretion, and fluid balance, all of which are crucial for maintaining homeostasis. Renal physiology examines renal blood flow, glomerular filtration, and urine formation, ensuring the body’s internal environment remains stable.Renal Blood FlowThe kidneys receive about 20-25% of the cardiac output, typically around 1200 mL of blood per minute in an average adult. Blood flows into the kidneys through the renal...
358
01:28Glomerular Filtration Rate and its Regulation
4.4K
The Glomerular Filtration Rate (GFR) is a measure of kidney function, reflecting the volume of filtrate formed per minute in the kidneys. On average, GFR is approximately 125 mL/min in males and 105 mL/min in females. Maintaining a relatively constant GFR is essential for the kidneys to effectively regulate body fluid homeostasis and maintain extracellular stability.
GFR regulation involves two primary intrinsic controls: the myogenic and tubuloglomerular feedback mechanisms.
The myogenic...
GFR regulation involves two primary intrinsic controls: the myogenic and tubuloglomerular feedback mechanisms.
The myogenic...
4.4K
01:27Transducer Mechanism: Enzyme-Linked Receptors
3.5K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
3.5K
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
2.1K
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
2.1K