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| {{STRUCTURE_1tev| PDB=1tev | SCENE= }} | | {{STRUCTURE_1tev| PDB=1tev | SCENE= }} |
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| '''Crystal structure of the human UMP/CMP kinase in open conformation'''
| | ===Crystal structure of the human UMP/CMP kinase in open conformation=== |
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| ==Overview==
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| Human UMP/CMP kinase plays a crucial role in supplying precursors for nucleic acid synthesis by catalyzing the conversion of UMP, CMP, and dCMP into their diphosphate form. In addition, this kinase is an essential component of the activation cascade of medicinally relevant nucleoside analog prodrugs such as AraC, gemcitabine, and ddC. During the catalytic cycle the enzyme undergoes large conformational changes from open in the absence of substrates to closed in the presence of both phosphoryl donor and phosphoryl acceptor. Here we report the crystal structure of the substrate-free, open form of human UMP/CMP kinase. Comparison of the open structure with the closed state previously reported for the similar Dictyostelium discoideum UMP/CMP kinase reveals the conformational changes that occur upon substrate binding. We observe a classic example of induced fit where substrate-induced conformational changes in hinge residues result in rigid body movements of functional domains to form the catalytically competent state. In addition, a homology model of the human enzyme in the closed state based on the structure of D. discoideum UMP/CMP kinase aids to rationalize the substrate specificity of the human enzyme.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15163660}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15163660 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15163660}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Nmp binding region]] | | [[Category: Nmp binding region]] |
| [[Category: Ploop]] | | [[Category: Ploop]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:51:55 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 00:07:11 2008'' |
