Creatine kinase isoenzymes specificities: histidine 65 in human CK-BB, a role in protein stability, not in catalysis.

Abstract:

:Creatine kinases (CK) play a prominent role in cell energy distribution through an energy shuttle between mitochondria and other organelles. Human brain CK was cloned and overexpressed in COS-7 cells. We then deleted His-65 and/or Pro-66 situated near the center of a flexible loop as shown by X-ray crystallography on mitochondrial and cytosolic CK. The DeltaH65 mutant had nearly the same affinity for its substrates as wild isoenzyme, but its stability was very low. Unlike DeltaH65, DeltaH65P66 had a eightfold decreased affinity for creatine phosphate and was unable to dephosphorylate cyclocreatine phosphate. Our results demonstrate that, despite an overall similar shape of the proteins, this loop accounts for some subtle differences in isoenzyme functions.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Mourad-Terzian T,Steghens JP,Min KL,Collombel C,Bozon D

doi

10.1016/s0014-5793(00)01614-8

keywords:

subject

Has Abstract

pub_date

2000-06-09 00:00:00

pages

22-6

issue

1

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(00)01614-8

journal_volume

475

pub_type

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