spacer
spacer

PDBsum entry 1qh4

Go to PDB code: 
Top Page protein ligands metals Protein-protein interface(s) links
Transferase PDB id
1qh4
Jmol
Contents
Protein chains
380 a.a. *
Ligands
ACT ×6
Metals
_CA
Waters ×1467
* Residue conservation analysis

References listed in PDB file
Key reference
Title Crystal structure of brain-Type creatine kinase at 1.41 a resolution.
Authors M.Eder, U.Schlattner, A.Becker, T.Wallimann, W.Kabsch, K.Fritz-Wolf.
Ref. Protein Sci, 1999, 8, 2258-2269. [DOI no: 10.1110/ps.8.11.2258]
PubMed id 10595529
Abstract
Excitable cells and tissues like muscle or brain show a highly fluctuating consumption of ATP, which is efficiently regenerated from a large pool of phosphocreatine by the enzyme creatine kinase (CK). The enzyme exists in tissue--as well as compartment-specific isoforms. Numerous pathologies are related to the CK system: CK is found to be overexpressed in a wide range of solid tumors, whereas functional impairment of CK leads to a deterioration in energy metabolism, which is phenotypic for many neurodegenerative and age-related diseases. The crystal structure of chicken cytosolic brain-type creatine kinase (BB-CK) has been solved to 1.41 A resolution by molecular replacement. It represents the most accurately determined structure in the family of guanidino kinases. Except for the N-terminal region (2-12), the structures of both monomers in the biological dimer are very similar and closely resemble those of the other known structures in the family. Specific Ca2+-mediated interactions, found between two dimers in the asymmetric unit, result in structurally independent heterodimers differing in their N-terminal conformation and secondary structure. The high-resolution structure of BB-CK presented in this work will assist in designing new experiments to reveal the molecular basis of the multiple isoform-specific properties of CK, especially regarding different subcellular locations and functional interactions with other proteins. The rather similar fold shared by all known guanidino kinase structures suggests a model for the transition state complex of BB-CK analogous to the one of arginine kinase (AK). Accordingly, we have modeled a putative conformation of CK in the transition state that requires a rigid body movement of the entire N-terminal domain by rms 4 A from the structure without substrates.
Secondary reference #1
Title Transition state structure of arginine kinase: implications for catalysis of bimolecular reactions.
Authors G.Zhou, T.Somasundaram, E.Blanc, G.Parthasarathy, W.R.Ellington, M.S.Chapman.
Ref. Proc Natl Acad Sci U S A, 1998, 95, 8449-8454. [DOI no: 10.1073/pnas.95.15.8449]
PubMed id 9671698
Full text Abstract
Figure 2.
Fig. 2. Details of the active site. For clarity only atoms in the immediate neighborhood are shown with carbon-colored black, oxygen red, nitrogen dark blue, magnesium light blue, sulfur yellow and phosphorus gray. Distances are shown in Å. (a) Stereo diagram comparing part of the experimental analog structure with omit-map electron density and the structure of the presumptive transition state (gray atoms). Small molecule model systems suggest a preassociative concerted phosphoryl transfer and a pentavalent -phosphorus transition state with about 20% covalent bonding to both the -phosphoryl oxygen and guanidino nitrogen (32, 33). The transition-state coordinates were derived from the experimental coordinates by replacing the nitrate with a phosphoryl group, and refining with additional distance and angle restraints appropriate for the estimated 20% partial covalent bonding. (b-e) Details of the enzyme-substrate analog interactions: (b) and phosphoryl groups of the ADP are held in place by extensive hydrogen bonds/salt bridges with four highly conserved arginines; (c) the nitrate (mimicking a planar phosphoryl group during transfer) is sandwiched between two conserved arginines and the Mg2+ ion whose position is constrained by ligands from the and phosphoryl groups of the ADP; (d) the guanidinium of the substrate arginine is clamped with salt bridges/hydrogen bonds to two carboxylates and a conserved cysteine that likely exists as a thiolate (54); and (e) interactions of the substrate amino and carboxylate groups with loop residues 63-68 of the enzyme. The carboxylate-to-backbone interactions might be conserved between all phosphagens and their kinases. The amino groups are present in arginine and lombricine but absent from creatine and glycocyamine. The tyrosine interacting with the amino group is conserved among AKs, but is a valine in all other phosphagen kinases. Immediately preceding residue 61 (and interactions with the carboxylate) is an insertion in other sequences whose size inversely correlates with the size of substrate (42).
Figure 3.
Fig. 3. Roles of neighboring amino acids in the catalytic mechanism of AK: (a) the forward reaction and (b) the reverse reaction. In this schematic representation, only the reactive groups of participants are shown. *, The structure does not indicate whether it is Glu-225 or Glu-314 that acts as the proposed acid/base catalyst.
Secondary reference #2
Title Structure of mitochondrial creatine kinase.
Authors K.Fritz-Wolf, T.Schnyder, T.Wallimann, W.Kabsch.
Ref. Nature, 1996, 381, 341-345.
PubMed id 8692275
Abstract
PROCHECK
Go to PROCHECK summary
 Headers