4r1r
From Proteopedia
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| - | [[Image:4r1r.gif|left|200px]]<br /><applet load="4r1r" size=" | + | [[Image:4r1r.gif|left|200px]]<br /><applet load="4r1r" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="4r1r, resolution 3.2Å" /> | caption="4r1r, resolution 3.2Å" /> | ||
'''RIBONUCLEOTIDE REDUCTASE R1 PROTEIN WITH SUBSTRATE, GDP AND EFFECTOR DTTP FROM ESCHERICHIA COLI'''<br /> | '''RIBONUCLEOTIDE REDUCTASE R1 PROTEIN WITH SUBSTRATE, GDP AND EFFECTOR DTTP FROM ESCHERICHIA COLI'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 4R1R is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with TTP and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] Known structural/functional Sites: <scene name='pdbsite=ACA:Active Site, w. Substrate Gdp, The Redox Center, CYS A 2 ...'>ACA</scene>, <scene name='pdbsite=ACB:Active Site, w. Substrate Gdp, The Redox Center, CYS B 2 ...'>ACB</scene>, <scene name='pdbsite=ACG:Active Site, w. Substrate Gdp, The Redox Center, CYS C 2 ...'>ACG</scene>, <scene name='pdbsite=SEE:Specificity Site w. Dttp. Observe That The Structure In ...'>SEE</scene>, <scene name='pdbsite=SEI:Specificity Site w. Dttp. Observe That The Structure In ...'>SEI</scene> and <scene name='pdbsite=SES:Specificity Site w. Dttp. Observe That The Structure In ...'>SES</scene>. Full crystallographic information is available from [http:// | + | 4R1R is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=TTP:'>TTP</scene> and <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] Known structural/functional Sites: <scene name='pdbsite=ACA:Active+Site,+w.+Substrate+Gdp,+The+Redox+Center,+CYS+A+2+...'>ACA</scene>, <scene name='pdbsite=ACB:Active+Site,+w.+Substrate+Gdp,+The+Redox+Center,+CYS+B+2+...'>ACB</scene>, <scene name='pdbsite=ACG:Active+Site,+w.+Substrate+Gdp,+The+Redox+Center,+CYS+C+2+...'>ACG</scene>, <scene name='pdbsite=SEE:Specificity+Site+w.+Dttp.+Observe+That+The+Structure+In+...'>SEE</scene>, <scene name='pdbsite=SEI:Specificity+Site+w.+Dttp.+Observe+That+The+Structure+In+...'>SEI</scene> and <scene name='pdbsite=SES:Specificity+Site+w.+Dttp.+Observe+That+The+Structure+In+...'>SES</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1R OCA]. |
==Reference== | ==Reference== | ||
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[[Category: specificity]] | [[Category: specificity]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:53:07 2008'' |
Revision as of 08:53, 3 February 2008
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RIBONUCLEOTIDE REDUCTASE R1 PROTEIN WITH SUBSTRATE, GDP AND EFFECTOR DTTP FROM ESCHERICHIA COLI
Overview
BACKGROUND: Ribonucleotide reductase (RNR) is an essential enzyme in DNA, synthesis, catalyzing all de novo synthesis of deoxyribonucleotides. The, enzyme comprises two dimers, termed R1 and R2, and contains the redox, active cysteine residues, Cys462 and Cys225. The reduction of, ribonucleotides to deoxyribonucleotides involves the transfer of free, radicals. The pathway for the radical has previously been suggested from, crystallographic results, and is supported by site-directed mutagenesis, studies. Most RNRs are allosterically regulated through two different, nucleotide-binding sites: one site controls general activity and the other, controls substrate specificity. Our aim has been to crystallographically, demonstrate substrate binding and to locate the two effector-binding, sites. RESULTS: We report here the first crystal structure of RNR R1 in a, reduced form. The structure shows that upon reduction of the redox active, cysteines, the sulfur atom of Cys462 becomes deeply buried. The more, accessible Cys225 moves to the former position of Cys462 making room for, the substrate. In addition, the structures of R1 in complexes with, effector, effector analog and effector plus substrate provide information, about these binding sites. The substrate GDP binds in a cleft between two, domains with its beta-phosphate bound to the N termini of two helices; the, ribose forms hydrogen bonds to conserved residues. Binding of dTTP at the, allosteric substrate specificity site stabilizes three loops close to the, dimer interface and the active site, whereas the general allosteric, binding site is positioned far from the active site. CONCLUSIONS: Binding, of substrate at the active site of the enzyme is structurally regulated in, two ways: binding of the correct substrate is regulated by the binding of, allosteric effectors and binding of the actual substrate occurs primarily, when the active-site cysteines are reduced. One of the loops stabilized, upon binding of dTTP participates in the formation of the, substrate-binding site through direct interaction with the nucleotide, base. The general allosteric effector site, located far from the active, site, appears to regulate subunit interactions within the holoenzyme.
About this Structure
4R1R is a Protein complex structure of sequences from Escherichia coli with and as ligands. Active as Ribonucleoside-diphosphate reductase, with EC number 1.17.4.1 Known structural/functional Sites: , , , , and . Full crystallographic information is available from OCA.
Reference
Binding of allosteric effectors to ribonucleotide reductase protein R1: reduction of active-site cysteines promotes substrate binding., Eriksson M, Uhlin U, Ramaswamy S, Ekberg M, Regnstrom K, Sjoberg BM, Eklund H, Structure. 1997 Aug 15;5(8):1077-92. PMID:9309223
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