Biology:Cystatin C

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Cystatin C or cystatin 3 (formerly gamma trace, post-gamma-globulin, or neuroendocrine basic polypeptide),[1] a protein encoded by the CST3 gene, is mainly used as a biomarker of kidney function. Recently, it has been studied for its role in predicting new-onset or deteriorating cardiovascular disease. It also seems to play a role in brain disorders involving amyloid (a specific type of protein deposition), such as Alzheimer's disease. In humans, all cells with a nucleus (cell core containing the DNA) produce cystatin C as a chain of 120 amino acids. It is found in virtually all tissues and body fluids. It is a potent inhibitor of lysosomal proteinases (enzymes from a special subunit of the cell that break down proteins) and probably one of the most important extracellular inhibitors of cysteine proteases (it prevents the breakdown of proteins outside the cell by a specific type of protein degrading enzymes). Cystatin C belongs to the type 2 cystatin gene family.

Role in medicine

Kidney function

Glomerular filtration rate (GFR), a marker of kidney health, is most accurately measured by injecting compounds such as inulin, radioisotopes such as 51chromium-EDTA, 125I-iothalamate, 99mTc-DTPA or radiocontrast agents such as iohexol, but these techniques are complicated, costly, time-consuming and have potential side-effects.[2][3] Creatinine is the most widely used biomarker of kidney function. It is inaccurate at detecting mild renal impairment, and levels can vary with muscle mass but not with protein intake. Urea levels might change with protein intake.[4] Formulas such as the Cockcroft and Gault formula and the MDRD formula (see Renal function) try to adjust for these variables.

Cystatin C has a low molecular weight (approximately 13.3 kilodaltons), and it is removed from the bloodstream by glomerular filtration in the kidneys. If kidney function and glomerular filtration rate decline, the blood levels of cystatin C rise. Cross-sectional studies (based on a single point in time) suggest that serum levels of cystatin C are a more precise test of kidney function (as represented by the glomerular filtration rate, GFR) than serum creatinine levels.[3][5] Longitudinal studies (following cystatin C over time) are sparse, but some show promising results.[6][7][8] Although studies are somewhat divergent, most studies find that cystatin C levels are less dependent on age, gender, ethnicity, diet, and muscle mass compared to creatinine,[9][10] and that cystatin C is equal or superior to the other available biomarkers in a range of different patient populations, including diabetic patients, in chronic kidney disease (CKD), and after kidney transplant.[11] It has been suggested that cystatin C might predict the risk of developing CKD, thereby signaling a state of 'preclinical' kidney dysfunction.[12] Additionally, the age-related rise in serum cystatin C is a powerful predictor of adverse age-related health outcomes, including all-cause mortality, death from cardiovascular disease, multimorbidity, and declining physical and cognitive function.[13] The UK's National Institute for Health and Care Excellence (NICE) guideline for the assessment and management of CKD in adults concluded that using serum cystatin C to estimate GFR is more specific for important disease outcomes than use of serum creatinine, and may reduce overdiagnosis in patients with a borderline diagnosis, reducing unnecessary appointments, patient worries, the overall burden of CKD in the population.[14]

Studies have also investigated cystatin C as a marker of kidney function in the adjustment of medication dosages.[15][16]

Cystatin C levels have been reported to be altered in patients with cancer,[17][18][19] (even subtle) thyroid dysfunction[20][21][22] and glucocorticoid therapy in some[23][24] but not all[25] situations. Other reports have found that levels are influenced by cigarette smoking and levels of C-reactive protein.[26] However, inflammation does not cause an increase in the production of cystatin C, since elective surgical procedures, producing a strong inflammatory response in patients, do not change the plasma concentration of cystatin C. Levels seem to be increased in HIV infection, which might or might not reflect actual renal dysfunction.[27][28][29] The role of cystatin C to monitor GFR during pregnancy remains controversial.[30][31] Like creatinine, the elimination of cystatin C via routes other than the kidney increase with worsening GFR.[32]

Death and cardiovascular disease

Kidney dysfunction increases the risk of death and cardiovascular disease.[33][34] Several studies have found that increased levels of cystatin C are associated with the risk of death, several types of cardiovascular disease (including myocardial infarction, stroke, heart failure, peripheral arterial disease and metabolic syndrome) and healthy aging.[citation needed][clarification needed] Some studies have found cystatin C to be better in this regard than serum creatinine or creatinine-based GFR equations.[35][36][37][38][39][40][41][42][43][44][45][46] Because the association of cystatin C with long term outcomes has appeared stronger than what could be expected for GFR, it has been hypothesized that cystatin C might also be linked to mortality in a way independent of kidney function.[47] In keeping with its housekeeping gene properties, it has been suggested that cystatin C might be influenced by the basal metabolic rate.[48]

Proposed shrunken pore syndrome

The glomerular sieving coefficients for 10–30 kDa plasma proteins in the human kidney are relatively high with coefficients between 0.9 and 0.07.[49] These relatively high sieving coefficients, combined with the high production of ultrafiltrate in health, means that proteins less than or equal to 30 kDa in plasma normally are mainly cleared by the kidneys and at least 85% of the clearance of cystatin C occurs in the kidney.[50] If the pores of the glomerular membrane shrink, the filtration of bigger molecules, e.g. cystatin C, will decrease, whereas the filtration of small molecules, like water and creatinine, will be less affected. In this case, cystatin C-based estimates of GFR, eGFRcystatin C, will be lower than creatinine-based estimates eGFRcreatinine, so that a hypothesized condition, named shrunken pore syndrome, is identified by a low eGFRcystatin C/eGFRcreatinine-ratio.[51] This syndrome is associated with a very strong increase in mortality.[52]

Neurologic disorders

Mutations in the cystatin 3 gene are responsible for the Icelandic type of hereditary cerebral amyloid angiopathy, a condition predisposing to intracerebral haemorrhage, stroke and dementia.[53][54] The condition is inherited in a dominant fashion. The monomeric cystatin C forms dimers and oligomers by domain swapping[55] and the structures of both the dimers[56] and oligomers[57] have been determined.

Since cystatin 3 also binds amyloid β and reduces its aggregation and deposition, it is a potential target in Alzheimer's disease.[58][59] Although not all studies have confirmed this, the overall evidence is in favor of a role for CST3 as a susceptibility gene for Alzheimer's disease.[60] Cystatin C levels have been reported to be higher in subjects with Alzheimer's disease.[61]

The role of cystatin C in multiple sclerosis and other demyelinating diseases (characterized by a loss of the myelin nerve sheath) remains controversial.[62]

Other roles

Cystatin C levels are decreased in atherosclerotic (so-called 'hardening' of the arteries) and aneurysmal (saccular bulging) lesions of the aorta.[63][64][65][66] Genetic and prognostic studies also suggest a role for cystatin C.[67][68] Breakdown of parts of the vessel wall in these conditions is thought to result from an imbalance between proteinases (cysteine proteases and matrix metalloproteinases, increased) and their inhibitors (such as cystatin C, decreased).

A few studies have looked at the role of cystatin C or the CST3 gene in age-related macular degeneration.[69][70] Cystatin C has also been investigated as a prognostic marker in several forms of cancer.[71][72] Its role in pre-eclampsia remains to be confirmed.[73][74][75][76]

Laboratory measurement

Cystatin C can be measured in a random sample of serum (the fluid in blood from which the red blood cells and clotting factors have been removed) using immunoassays such as nephelometry or particle-enhanced turbidimetry.[77] It is a more expensive test than serum creatinine (around $2 or $3, compared to $0.02 to $0.15), which can be measured with a Jaffe reaction.[78][79][80]

Reference values differ in many populations and with sex and age. Across different studies, the mean reference interval (as defined by the 5th and 95th percentile) was between 0.52 and 0.98 mg/L. For women, the average reference interval is 0.52 to 0.90 mg/L with a mean of 0.71 mg/L. For men, the average reference interval is 0.56 to 0.98 mg/L with a mean of 0.77 mg/L.[77] The normal values decrease until the first year of life, remaining relatively stable before they increase again, especially beyond age 50.[81][82][83] Creatinine levels increase until puberty and differ according to gender from then on, making their interpretation problematic for pediatric patients.[82][84]

In a large study from the United States National Health and Nutrition Examination Survey, the reference interval (as defined by the 1st and 99th percentile) was between 0.57 and 1.12 mg/L. This interval was 0.55 - 1.18 for women and 0.60 - 1.11 for men. Non-Hispanic blacks and Mexican Americans had lower normal cystatin C levels.[81] Other studies have found that in patients with an impaired renal function, women have lower and blacks have higher cystatin C levels for the same GFR.[85] For example, the cut-off values of cystatin C for CKD for a 60-year-old white women would be 1.12 mg/L and 1.27 mg/L in a black man (a 13% increase). For serum creatinine values adjusted with the MDRD equation, these values would be 0.95 mg/dL to 1.46 mg/dL (a 54% increase).[86]

Based on a threshold level of 1.09 mg/L (the 99th percentile in a population of 20- to 39-year-olds without hypertension, diabetes, microalbuminuria or macroalbuminuria or higher than stage 3 chronic kidney disease), the prevalence of increased levels of cystatin C in the United States was 9.6% in subjects of normal weight, increasing in overweight and obese individuals.[87] In Americans aged 60 and 80 and older, serum cystatin is increased in 41% and more than 50%.[81]

Molecular biology

The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. The cystatin locus on the short arm of chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes.

The CST3 gene is located in the cystatin locus and comprises 3 exons (coding regions, as opposed to introns, non-coding regions within a gene), spanning 4.3 kilo-base pairs. It encodes the most abundant extracellular inhibitor of cysteine proteases. It is found in high concentrations in biological fluids and is expressed in virtually all organs of the body (CST3 is a housekeeping gene). The highest levels are found in semen, followed by breastmilk, tears and saliva. The hydrophobic leader sequence indicates that the protein is normally secreted. There are three polymorphisms in the promoter region of the gene, resulting in two common variants.[88] Several single nucleotide polymorphisms have been associated with altered cystatin C levels.[89]

Cystatin C is a non-glycosylated, basic protein (isoelectric point at pH 9.3). The crystal structure of cystatin C is characterized by a short alpha helix and a long alpha helix which lies across a large antiparallel, five-stranded beta sheet. Like other type 2 cystatins, it has two disulfide bonds. Around 50% of the molecules carry a hydroxylated proline. Cystatin C forms dimers (molecule pairs) by exchanging subdomains; in the paired state, each half is made up of the long alpha helix and one beta strand of one partner, and four beta strands of the other partner.[90]

History

Cystatin C was first described as 'gamma-trace' in 1961 as a trace protein together with other ones (such as beta-trace) in the cerebrospinal fluid and in the urine of people with kidney failure.[91] Grubb and Löfberg first reported its amino acid sequence.[91] They noticed it was increased in patients with advanced kidney failure.[92] It was first proposed as a measure of glomerular filtration rate by Grubb and coworkers in 1985.[93][94]

Use of serum creatinine and cystatin C was found very effective in accurately reflecting the GFR in a study reported in the July 5, 2012 issue of the New England Journal of Medicine.[95]

References

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  2. ↑ "Can cystatin C replace creatinine to estimate glomerular filtration rate? A literature review". American Journal of Nephrology 27 (2): 197–205. 2007. doi:10.1159/000100907. PMID 17361076. https://www.karger.com/Article/PDF/000100907. 
  3. ↑ 3.0 3.1 "Diagnostic accuracy of cystatin C compared to serum creatinine for the estimation of renal dysfunction in adults and children--a meta-analysis". Clinical Biochemistry 40 (5–6): 383–91. March 2007. doi:10.1016/j.clinbiochem.2006.10.026. PMID 17316593. 
  4. ↑ "Dietary protein and renal function". Journal of the American Society of Nephrology 3 (11): 1723–37. May 1993. doi:10.1681/ASN.V3111723. PMID 8329667. http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=8329667. 
  5. ↑ "Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis". American Journal of Kidney Diseases 40 (2): 221–6. August 2002. doi:10.1053/ajkd.2002.34487. PMID 12148093. 
  6. ↑ "Serial measurements of cystatin C are more accurate than creatinine-based methods in detecting declining renal function in type 1 diabetes". Diabetes Care 31 (5): 971–3. May 2008. doi:10.2337/dc07-1588. PMID 18319326. http://care.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=18319326. 
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  49. ↑ [non-primary source needed] "Glomerular protein sieving and implications for renal failure in Fanconi syndrome". Kidney International 60 (5): 1885–92. November 2001. doi:10.1046/j.1523-1755.2001.00016.x. PMID 11703607. 
  50. ↑ [non-primary source needed] "Renal handling of radiolabelled human cystatin C in the rat". Scandinavian Journal of Clinical and Laboratory Investigation 56 (5): 409–14. August 1996. doi:10.3109/00365519609088795. PMID 8869663. 
  51. ↑ [non-primary source needed] "Reduction in glomerular pore size is not restricted to pregnant women. Evidence for a new syndrome: 'Shrunken pore syndrome'". Scandinavian Journal of Clinical and Laboratory Investigation 75 (4): 333–40. July 2015. doi:10.3109/00365513.2015.1025427. PMID 25919022. 
  52. ↑ "Shrunken pore syndrome - a common kidney disorder with high mortality. Diagnosis, prevalence, pathophysiology and treatment options". Clinical Biochemistry Online ahead of print: 12–20. June 2020. doi:10.1016/j.clinbiochem.2020.06.002. PMID 32544475. 
  53. ↑ "Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteases". The Journal of Experimental Medicine 169 (5): 1771–8. May 1989. doi:10.1084/jem.169.5.1771. PMID 2541223. 
  54. ↑ "The role of cystatin C in cerebral amyloid angiopathy and stroke: cell biology and animal models". Brain Pathology 16 (1): 60–70. January 2006. doi:10.1111/j.1750-3639.2006.tb00562.x. PMID 16612983. 
  55. ↑ "Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping". Nature Structural Biology 8 (4): 316–320. April 2001. doi:10.1038/86188. PMID 11276250. https://lup.lub.lu.se/record/131360. 
  56. ↑ "Glomerular protein sieving and implications for renal failure in Fanconi syndrome". Proteins 61 (3): 570–578–92. Nov 2005. doi:10.1002/prot.20633. PMID 16170782. 
  57. ↑ "Structural characterization of covalently stabilized human cystatin C oligomers". International Journal of Molecular Sciences 21 (5860): 5860. Aug 2020. doi:10.3390/ijms21165860. PMID 32824145. 
  58. ↑ "Cystatin C inhibits amyloid-beta deposition in Alzheimer's disease mouse models". Nature Genetics 39 (12): 1440–2. December 2007. doi:10.1038/ng.2007.29. PMID 18026100. 
  59. ↑ "Cystatin C modulates cerebral beta-amyloidosis". Nature Genetics 39 (12): 1437–9. December 2007. doi:10.1038/ng.2007.23. PMID 18026102. 
  60. ↑ "Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database". Nature Genetics 39 (1): 17–23. January 2007. doi:10.1038/ng1934. PMID 17192785. 
  61. ↑ "Genotype and plasma concentration of cystatin C in patients with late-onset Alzheimer disease". Dementia and Geriatric Cognitive Disorders 23 (4): 251–7. 2007. doi:10.1159/000100021. PMID 17310123. https://www.karger.com/Article/PDF/000100021. 
  62. ↑ "Cleavage of cystatin C is not associated with multiple sclerosis". Annals of Neurology 62 (2): 201–4; discussion 205. August 2007. doi:10.1002/ana.20968. PMID 17006926. 
  63. ↑ "Cystatin C deficiency in human atherosclerosis and aortic aneurysms". The Journal of Clinical Investigation 104 (9): 1191–7. November 1999. doi:10.1172/JCI7709. PMID 10545518. PMC 409823. https://dash.harvard.edu/bitstream/handle/1/13506934/Cystatin%20C%20deficiency%20in%20human%20atherosclerosis.pdf?sequence=1. 
  64. ↑ "Cysteine protease activity in the wall of abdominal aortic aneurysms". Journal of Vascular Surgery 46 (6): 1260–6. December 2007. doi:10.1016/j.jvs.2007.08.015. PMID 18155003. 
  65. ↑ "Collagen degradation in the abdominal aneurysm: a conspiracy of matrix metalloproteinase and cysteine collagenases". The American Journal of Pathology 170 (3): 809–17. March 2007. doi:10.2353/ajpath.2007.060522. PMID 17322367. PMC 1864891. http://ajp.amjpathol.org/cgi/pmidlookup?view=long&pmid=17322367.  [|permanent dead link|dead link}}]
  66. ↑ "Distribution, activity and concentration of cathepsin B and cystatin C in the wall of aortic aneurysm". Polish Journal of Pathology 50 (2): 83–6. 1999. PMID 10481531. 
  67. ↑ "Genetic approach to the role of cysteine proteases in the expansion of abdominal aortic aneurysms". The British Journal of Surgery 91 (1): 86–9. January 2004. doi:10.1002/bjs.4364. PMID 14716800. 
  68. ↑ "Cystatin C deficiency is associated with the progression of small abdominal aortic aneurysms". The British Journal of Surgery 88 (11): 1472–5. November 2001. doi:10.1046/j.0007-1323.2001.01911.x. PMID 11683743. 
  69. ↑ "CST3 genotype associated with exudative age related macular degeneration". The British Journal of Ophthalmology 86 (2): 214–9. February 2002. doi:10.1136/bjo.86.2.214. PMID 11815350. 
  70. ↑ "The role of cathepsins in ocular physiology and pathology". Experimental Eye Research 84 (3): 383–8. March 2007. doi:10.1016/j.exer.2006.05.017. PMID 16893541. 
  71. ↑ "Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis". British Journal of Cancer 90 (10): 1961–8. May 2004. doi:10.1038/sj.bjc.6601830. PMID 15138478. 
  72. ↑ "Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis". Clinical Cancer Research 6 (2): 505–11. February 2000. PMID 10690531. http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=10690531. 
  73. ↑ "Serum cystatin C reflects glomerular endotheliosis in normal, hypertensive and pre-eclamptic pregnancies". BJOG 110 (9): 825–30. September 2003. doi:10.1111/j.1471-0528.2003.02051.x. PMID 14511964. 
  74. ↑ "Cystatin C and preeclampsia: a case control study". Renal Failure 30 (1): 89–95. 2008. doi:10.1080/08860220701742229. PMID 18197549. 
  75. ↑ "Cystatin C, beta-2-microglobulin and beta-trace protein in pre-eclampsia". Acta Obstetricia et Gynecologica Scandinavica 86 (8): 921–6. 2007. doi:10.1080/00016340701318133. PMID 17653875. 
  76. ↑ "Increased cystatin C expression in the pre-eclamptic placenta". Molecular Human Reproduction 13 (3): 189–95. March 2007. doi:10.1093/molehr/gal111. PMID 17227816. 
  77. ↑ 77.0 77.1 "Adult cystatin C reference intervals determined by nephelometric immunoassay". Clinical Biochemistry 40 (13–14): 1084–7. September 2007. doi:10.1016/j.clinbiochem.2007.05.011. PMID 17624320. 
  78. ↑ "Serum cystatin C may be a better marker of renal impairment than creatinine". Journal of the American Geriatrics Society 51 (11): 1674; author reply 1674-5. November 2003. doi:10.1046/j.1532-5415.2003.515244.x. PMID 14687406. 
  79. ↑ "Measurement of serum creatinine--current status and future goals". The Clinical Biochemist. Reviews 27 (4): 173–84. November 2006. PMID 17581641. 
  80. ↑ "Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program". Clinical Chemistry 52 (1): 5–18. January 2006. doi:10.1373/clinchem.2005.0525144. PMID 16332993. 
  81. ↑ 81.0 81.1 81.2 "Serum cystatin C in the United States: the Third National Health and Nutrition Examination Survey (NHANES III)". American Journal of Kidney Diseases 51 (3): 385–94. March 2008. doi:10.1053/j.ajkd.2007.11.019. PMID 18295054. 
  82. ↑ 82.0 82.1 "Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children". Archives of Disease in Childhood 82 (1): 71–5. January 2000. doi:10.1136/adc.82.1.71. PMID 10630919. 
  83. ↑ "Cystatin C reference values and aging". Clinical Biochemistry 39 (6): 658–61. June 2006. doi:10.1016/j.clinbiochem.2006.03.017. PMID 16730690. 
  84. ↑ "Cystatin C as a marker of GFR--history, indications, and future research". Clinical Biochemistry 38 (1): 1–8. January 2005. doi:10.1016/j.clinbiochem.2004.09.025. PMID 15607309. 
  85. ↑ "Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD". American Journal of Kidney Diseases 51 (3): 395–406. March 2008. doi:10.1053/j.ajkd.2007.11.018. PMID 18295055. 
  86. ↑ "Cystatin C: research priorities targeted to clinical decision making". American Journal of Kidney Diseases 51 (3): 358–61. March 2008. doi:10.1053/j.ajkd.2008.01.002. PMID 18295049. 
  87. ↑ "Overweight, obesity, and elevated serum cystatin C levels in adults in the United States". The American Journal of Medicine 121 (4): 341–8. April 2008. doi:10.1016/j.amjmed.2008.01.003. PMID 18374694. 
  88. ↑ "Entrez Gene: CST3 cystatin C (amyloid angiopathy and cerebral hemorrhage)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1471. 
  89. ↑ "A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study". BMC Medical Genetics 8 (Suppl 1): S10. September 2007. doi:10.1186/1471-2350-8-S1-S10. PMID 17903292. 
  90. ↑ "Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping". Nature Structural Biology 8 (4): 316–20. April 2001. doi:10.1038/86188. PMID 11276250. http://portal.research.lu.se/ws/files/4833049/624200.pdf. 
  91. ↑ 91.0 91.1 "Human gamma-trace, a basic microprotein: amino acid sequence and presence in the adenohypophysis". Proceedings of the National Academy of Sciences of the United States of America 79 (9): 3024–7. May 1982. doi:10.1073/pnas.79.9.3024. PMID 6283552. Bibcode: 1982PNAS...79.3024G. 
  92. ↑ "Quantitation of gamma-trace in human biological fluids: indications for production in the central nervous system". Scandinavian Journal of Clinical and Laboratory Investigation 39 (7): 619–26. November 1979. doi:10.3109/00365517909108866. PMID 119302. 
  93. ↑ "Serum concentration of cystatin C, factor D and beta 2-microglobulin as a measure of glomerular filtration rate". Acta Medica Scandinavica 218 (5): 499–503. 1985. doi:10.1111/j.0954-6820.1985.tb08880.x. PMID 3911736. 
  94. ↑ "The blood serum concentration of cystatin C (gamma-trace) as a measure of the glomerular filtration rate". Scandinavian Journal of Clinical and Laboratory Investigation 45 (2): 97–101. April 1985. doi:10.3109/00365518509160980. PMID 3923607. 
  95. ↑ "Cystatin C versus creatinine in determining risk based on kidney function". The New England Journal of Medicine 369 (10): 932–43. September 2013. doi:10.1056/NEJMoa1214234. PMID 24004120. 

External links

  • The MEROPS online database for peptidases and their inhibitors: I25.004
  • Overview of all the structural information available in the PDB for UniProt: P01034 (Cystatin-C) at the PDBe-KB.



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