Crystallographic refinement by simulated annealing: application to crambin

Brünger, A.T.; Karplus, Martin; Petsko, Gregory A.

doi:10.1107/s0108767388009195

Cited by 293 publications

(169 citation statements)

References 23 publications

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“…The structures were refined with XPLOR (Briinger, 1989) (X-PLOR: A System for X-ray Crystallography and NMR, Version 3.1, Yale University Press, New Haven, CT) beginning with the crystal structure of the HONH-iBM-Ala-Gly-NH2/MMP-8 complex (Grams et al, 1995b). Data and refinement statistics are summarized in Table 3.…”

Section: Refinementmentioning

confidence: 99%

Structure of malonic acid‐based inhibitors bound to human neutrophil collagenase. A new binding mode explains apparently anomalous data

et al. 1998

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Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases, which have been implicated in various disease processes. Various classes of MMP inhibitors, including hydroxamic acids, phosphinic acids, and thiols, have been previously described. Most of these mimic peptides, and most likely bind analogous to the corresponding peptide substrates. Among the hydroxamic acids, malonic acid derivatives have been used as MMP inhibitors, although optimization of their inhibition potency was not successful. Here we report the design of malonic acid-based inhibitors using the X-ray structure of a collagenase/inhibitor complex, which revealed a nonsubstrate-like binding mode. The proposed P-type turn-like conformation for the improved inhibitors was confirmed by X-ray crystallography. The observation of nonsubstrate-like binding confirms the original strategy for structure-based modeling of improved malonic acid inhibitors, and explains kinetic data that are inconsistent with substrate-like binding. Detailed interactions for the improved inhibitors seen in the crystal structure also suggest possibilities for further modifications in cycles of structure based drug design. Indeed, we have designed nonpeptidic inhibitors with approximately 500-fold improved inhibition based on these structures.

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Section: Refinementmentioning

confidence: 99%

Structure of malonic acid‐based inhibitors bound to human neutrophil collagenase. A new binding mode explains apparently anomalous data

et al. 1998

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“…Model building was carried out with the program 0 (Jones et al, 1991), and crystallographic refinement was carried out using X-PLOR (Briinger, 1989). In order to monitor progress of the refinement by means of the free R-factor (Briinger, 1992).…”

mentioning

confidence: 99%

Crystal structure of the reduced Schiff‐base intermediate complex of transaldolase B from escherichia coli: Mechanistic implications for class I aldolases

et al. 1997

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Transaldolase catalyzes transfer of a dihydroxyacetone moiety from a ketose donor to an aldose acceptor. During catalysis, a Schiff-base intermediate between dihydroxyacetone and the €-amino group of a lysine residue at the active site of the enzyme is formed. This Schiff-base intermediate has been trapped by reduction with potassium borohydride, and the crystal structure of this complex has been determined at 2.2 a resolution. The overall structures of the complex and the native enzyme are very similar; formation of the intermediate induces no large conformational changes. The dihydroxyacetone moiety is covalently linked to the side chain of Lys 132 at the active site of the enzyme. The C1 hydroxyl group of the dihydroxyacetone moiety forms hydrogen bonds to the side chains of residues Asn 154 and Ser 176. The C3 hydroxyl group interacts with the side chain of Asp 17 and Asn 35. Based on the crystal structure of this complex a reaction mechanism for transaldolase is proposed.

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“…The model obtained was then subjected to rigid body refinement using the program XPLOR [25]. In this case each secondary structure and loop was treated as a rigid body.…”

Section: Rejinement Of Modelmentioning

confidence: 99%

Crystal structure of apo‐glycolate oxidase

Sandalova

Lindqvist

1993

FEBS Letters

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The crystal structure of the apoform of the a&barrel enzyme glycoiate oxidase has been determined to 2.6 A resolution. Removal of the tightly bound cofactor FMN has a very strong influence on the protein structure; it is converted into a very flexible state, verging on a molten globule type of structure. The asymmetric unit contains two subunits with different conformations to each other and to the halo-enzyme. The secondary structures are preserved, but their mutual arrangement has changed to some extent introducing cavities into the protein. The largest structural shifts are, however, found in the loops.

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Crystallographic refinement by simulated annealing: application to crambin

Cited by 293 publications

References 23 publications

Structure of malonic acid‐based inhibitors bound to human neutrophil collagenase. A new binding mode explains apparently anomalous data

Structure of malonic acid‐based inhibitors bound to human neutrophil collagenase. A new binding mode explains apparently anomalous data

Crystal structure of the reduced Schiff‐base intermediate complex of transaldolase B from escherichia coli: Mechanistic implications for class I aldolases

Crystal structure of apo‐glycolate oxidase

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