Creatine Kinase

Creatine Kinase plays a key role in evergy metabolism in cells by catalyzing the reversible transfer of a phosphoryl group from phosphocreatine to MgADP to form creatine and MgATP.. 

                                                                     Creatine Phosphate

Phosphocreatine  +  MgADP      <=>    Creatine + MgATP

The protein is found in three places in animals: muscle, the heart, and the brain.  Creatine Kinase makes up 10-20% of the cytoplasm proteins in muscle cells.  Made up of eight subunits, this octomer has 379 residues per chain.  The molecular weight of the monomers 43138kD.  The monomer subunits are all identical.  Each monomer consists of a small alpha-helical domain and a large domain containing an eight-stranded antiparallel beta-sheet flanked by seven alpha-helices.   The octameric structure shown above is from the mitochondria of human muscle cells.   The protein was located in the intermembrane compartment and along the cristae membranes in the mitochondria.  Crystallography data states that the octameric unit appears as a cube with each side of the cube being 93 angstroms long.  The channel that goes through the middle of the octamer is 20 angstroms wide. 

Sequence and secondary structure
Below is the sequence of residues on the top lines with the letters below this sequence signifying secondary structures that the amino acids are in.  This is chain A of the octamer.

H    alpha helix (4-helix)

B     residue in isolated beta bridge

E     extended strand, participates in beta ladder

G    310 helix (3-helix)

I      pi helix (5-helix)

T     hydrogen bond turn

S     bend

1 MPFGNTHNKY KLNYKSEEEY PDLSKHNNHM AKVLTPDLYK KLRDKETPSG
TTTTHHHHS TT BHH HHHTTHHHHH HHTT TTS

51 FTLDDVIQTG VDNPGHPFIM TVGCVAGDEE SYTVFKDLFD PIIQDRHGGF
HHHHHTHH HH BTTB B B SSST HHHHTHHHHT HHHHHHTTS

101 KPTDKHKTDL NHENLKGGDD LDPHYVLSSR VRTGRSIKGY TLPPHCSRGE
TT GGGG S B TTTB EEE EEEEE BTTS TTTTTHHH

151 RRAVEKLSVE ALNSLTGEFK GKYYPLKSMT EQEQQQLIDD HFLFDKPVSP
HHHHHHHHHH HHTTTTGGG EEEEESTT HHHHHHHHTT T S H

201 LLLASGMARD WPDARGIWHN DNKSFLVWVN EEDHLRVISM EKGGNMKEVF
HHHTTTTTTT TTTT EEEEE TTSSEEEEES SSSSEEEEEE EESSBHHHHH

251 RRFCVGLQKI EEIFKKAGHP FMWNEHLGYV LTCPSNLGTG LRGGVHVKLA
HHHHHHHHHH HHHHHHTT B EETTTEE SBGGGTBT EEEEEEE T

301 HLSKHPKFEE ILTRLRLQKR GTSVFDTAAV GSVFDISNAD RLGSSEVEQV
TTTTTTTHHH HHHHHTEEEE EEEEEE SSS HHHHH

351 QLVVDGVKLM VEMEKKLEKG QSIDDMIPAQ K
HHHHHHHHHH HHHHHHHTTT SS

View Secondary Features:

Beta Sheets

The beta sheets cover half of the active site pocket.  Viewing the beta sheets of the A chain enables one to better see the 3 bound phosphates in the active site.

Alpha Helices

Viewing the alpha helices of the octamer helps one to see that the contacts made between the monomers are done through alpha helices.

View Primary Features:

Hydrogen Bonds On

Hydrogen Bonds Off

Hydrophobic Regions

Viewing the hydrophobic regions of the octamer show that the channel has hydrophobic residues protruding into the middle of it.  It also appears as if the the contacts made between the monomers occurs through some hydrophobic interactions.

Acidic Areas

Basic Areas

The active site has many basic groups protruding into it which can be best seen through viewing the monomer.

Charged Molecules

Again, looking at the active site shows the presence of charged molecules within it.  Positively charged groups in the active site help to bind the negatively charged ATP.

This is the A chain of the eight chain unit.  The active site is highlighted in yellow.  The active site is centered around Cystine 282.  All eight of the monomers show active sites in the same area.  Many lysine and arginine residues are located in the active site which provide it with a positive charge. 

References:

Buechter, D., Medzihradszky, K., Burlingame, A., and Kenyon, G.: The Active Site of Creatine Kinase - Affinity Labeling of Cysteine-282 with
N-(2,3-epoxypropyl)-N-amidinoglycine, J. Biol. Chem., 267, 2173 (1992).

Eder, M., Fritz-Wolf, K., Kabsch, W., Wallimann, T., Schlattner, U.: Crystal Structure of Human Ubiquitous Mitochondrial Creatine Kinase Proteins: Struct.,Funct., Genet. 39 pp. 216 (2000).

Rao, J. K., Bujacz, G., Wlodawer, A.: Crystal structure of rabbit muscle creatine kinase. FEBS Lett 439 pp. 133 (1998).

Wood, T. D., Guan, Z., Borders, C. L. Jr., Chen, L. H., Kenyon, G. L., McLafferty, F. W. . Creatine kinase: Essential arginine residues at the
nucleotide binding site identified by chemical modification and high-resolution tandem mass spectrometry. Proc. Natl. Acad. Sci. U. S. A. 95: 3362-3365. (1998)