Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer -typically found in the heart 5 Isoforms Know in the Body Mitochondrial (30% of enzymatic activity) 4.) Sarcomeric type ( s mtCK) -octamer 5.) Ubiquitous type ( u mtCK) -octamer Blum, H. E., Deus, B., and Gerok, W. (1983) Mitochondrial creatine kinase from human

Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer

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Creatine Kinase

Cystosolic (70% of enzymatic activity)

1.) Muscle type (CK-MM)

-homodimer

2.) Brain type (CK-BB)

-homodimer

3.) Hybrid type (CK-MB)

-heterodimer

-typically found in the heart

5 Isoforms Know in the Body

Mitochondrial (30% of enzymatic

activity)

4.) Sarcomeric type (smtCK)

-octamer

5.) Ubiquitous type (umtCK)

-octamer

Blum, H. E., Deus, B., and Gerok, W. (1983) Mitochondrial creatine kinase from human heart: purification and characterization of crystallized isoenzyme. J. Biol. Chem. 94, 1247-1257.

Page 2: Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer

Pathway

Tokasarska-Schlattner, M., Williann, T. (2006) Mitochondrial creatine kinase in human health and disease. Mol Bas. Dise. Vol 176, Iss 2, 164-180.

Page 3: Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer

Amino Acid Sequence Alignment

-Methionine 273-Cysteine 284

-Tryptophan 211, 218, and 228 Lyzlova, S. N., Stefanov, V. E. (1990) Phosphagen Kinases. CRC Press, 63-73 pgs.

Page 4: Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer

-Methionine 273-Cysteine 284

Amino Acid Sequence Alignment

Page 5: Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer

Amino Acid Sequence Alignment

-Tryptophan 211, 218, and 228

Page 6: Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer

Structure -13-18 alpha helicies depending on specific structure

-32-38% alpha helix residues-16-19 beta sheets

-15-16%

-Human CK-BB -Contains

-19 alpha helices (38%)

-18 beta sheets (16%)

PDB id = 3DRB

Bong, S. M., Chi, Y. M., Hwang, K. Y., Lee, K. S., Moon, J. H., and Nam, K. H. (2008) Structural studies of human brain-type creatine kinase complexed with ADP-Mg2+-NO3—

creatine trasition-state analogue complex. FEBS Lett. 582, 28, 3959-3965.

Page 7: Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer

Page 8: Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer

Page 9: Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer

Page 10: Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer

Page 11: Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer

Transition Complex

-Green loop interactions close off active site

-Arg 130,132,236,292,320 create a positive pocket for phosphate of ATP/ADP to bind

-Creatine’s carboxylate forms a H-bond with main chain N from Val72

-Cys283 anchors creatine for nucleophilic attach of a phosphorus from ATP

Bong, S. M., Chi, Y. M., Hwang, K. Y., Lee, K. S., Moon, J. H., and Nam, K. H. (2008) Structural studies of human brain-type creatine kinase complexed with ADP-Mg2+-NO3—creatine trasition-state analogue complex. FEBS Lett. 582, 28, 3959-3965.

Page 12: Creatine Kinase Cystosolic (70% of enzymatic activity) 1.) Muscle type (CK-MM) -homodimer 2.) Brain type (CK-BB) -homodimer 3.) Hybrid type (CK-MB) -heterodimer

Creatine Kinase Test

-Typical cardiac marker

- During myocardia infarction cell

contents is expelled

-Can be an indicator of several

other health issues

-Depends on what isoform is

elevated in the blood

-Stroke, pulmonary infection, muscular

dystrophies, myopathy, and others "Creatine Kinase, Serum." Mayo Clinic Mayo Medical Laboratories. January 1, 1999. Accessed October 19, 2014. http://www.mayomedicallaboratories.com/test-catalog/Clinical and Interpretive/8336.