X-ray structure of a human cardiac muscle troponin C/troponin I chimera in two crystal forms

The X-ray crystal structure of a human cardiac muscle troponin C/troponin I chimera has been determined in two different crystal forms and shows a conformation of the complex that differs from that previously observed by NMR. The chimera consists of the N-terminal domain of troponin C (cTnC; residues 1–80) fused to the switch region of troponin I (cTnI; residues 138–162). In both crystal forms, the cTnI residues form a six-turn α-helix that lays across the hydrophobic groove of an adjacent cTnC molecule in the crystal structure. In contrast to previous models, the cTnI helix runs in a parallel direction relative to the cTnC groove and completely blocks the calcium desensitizer binding site of the cTnC–cTnI interface.

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Solution structure of the regulatory domain of human cardiac troponin C in complex with the switch region of cardiac troponin I and W7: The basis of W7 as an inhibitor of cardiac muscle contraction

Journal of Molecular and Cellular Cardiology ◽

10.1016/j.yjmcc.2010.01.016 ◽

2010 ◽

Vol 48 (5) ◽

pp. 925-933 ◽

Cited By ~ 21

Author(s):

Marta Oleszczuk ◽

Ian M. Robertson ◽

Monica X. Li ◽

Brian D. Sykes

Keyword(s):

Muscle Contraction ◽

Cardiac Muscle ◽

Cardiac Troponin ◽

Solution Structure ◽

Troponin I ◽

Troponin C ◽

Regulatory Domain ◽

Switch Region ◽

Cardiac Troponin C ◽

Human Cardiac Troponin C

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Structure of the Regulatory Domain of Human Cardiac Troponin C in Complex with the Switch Region of Cardiac Troponin I and the Drug W7: The Basis of W7 as an Inhibitor of Cardiac Muscle Contraction

Biophysical Journal ◽

10.1016/j.bpj.2009.12.806 ◽

2010 ◽

Vol 98 (3) ◽

pp. 150a ◽

Cited By ~ 1

Author(s):

Marta Oleszczuk ◽

Ian M. Robertson ◽

Monica X. Li ◽

Brian D. Sykes

Keyword(s):

Muscle Contraction ◽

Cardiac Muscle ◽

Cardiac Troponin ◽

Troponin I ◽

Troponin C ◽

Cardiac Troponin I ◽

Regulatory Domain ◽

Switch Region ◽

Cardiac Troponin C ◽

Human Cardiac Troponin C

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Crystal Forms of Semisynthetic Ergot Alkaloid Terguride

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20020479 ◽

2002 ◽

Vol 67 (4) ◽

pp. 479-489 ◽

Cited By ~ 4

Author(s):

Michal Hušák ◽

Bohumil Kratochvíl ◽

Ivana Císařová ◽

Ladislav Cvak ◽

Alexandr Jegorov ◽

...

Keyword(s):

Crystal Structure ◽

Ergot Alkaloid ◽

Simplified Model ◽

Quantum Mechanical ◽

Quantum Mechanical Calculations ◽

X Ray Diffraction ◽

Torsion Angles ◽

Crystal Forms ◽

X Ray ◽

Independent Molecules

Two new structures of semisynthetic ergot alkaloid terguride created by unusual number of symmetry-independent molecules were determined by X-ray diffraction methods at 150 K. Form A (monoclinic, P212121, Z = 12) contains three symmetry-independent terguride molecules and two molecules of water in the asymmetric part of the unit cell. The form CA (monoclinic, P21, Z = 8) is an anhydrate remarkable by the presence of four symmetry-independent molecules in the crystal structure. Conformations of twelve symmetry-independent molecules that were found in four already described terguride structures are compared with torsion angles obtained by ab initio quantum-mechanical calculations for the simplified model of N-cyclohexyl-N'-diethylurea.

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The High Resolution Crystal Structure of the Human Tumor Suppressor Maspin Reveals a Novel Conformational Switch in the G-helix

Journal of Biological Chemistry ◽

10.1074/jbc.m412043200 ◽

2005 ◽

Vol 280 (23) ◽

pp. 22356-22364 ◽

Cited By ~ 50

Author(s):

Ruby H. P. Law ◽

James A. Irving ◽

Ashley M. Buckle ◽

Katya Ruzyla ◽

Marguerite Buzza ◽

...

Keyword(s):

Crystal Structure ◽

High Resolution ◽

Tumor Suppressor ◽

Physiological Role ◽

Human Tumor ◽

Salt Bridge ◽

Structural Data ◽

Crystal Forms ◽

Reactive Center ◽

Α Helix

Maspin is a serpin that acts as a tumor suppressor in a range of human cancers, including tumors of the breast and lung. Maspin is crucial for development, because homozygous loss of the gene is lethal; however, the precise physiological role of the molecule is unclear. To gain insight into the function of human maspin, we have determined its crystal structure in two similar, but non-isomorphous crystal forms, to 2.1- and 2.8-Å resolution, respectively. The structure reveals that maspin adopts the native serpin fold in which the reactive center loop is expelled fully from the A β-sheet, makes minimal contacts with the core of the molecule, and exhibits a high degree of flexibility. A buried salt bridge unique to maspin orthologues causes an unusual bulge in the region around the D and E α-helices, an area of the molecule demonstrated in other serpins to be important for cofactor recognition. Strikingly, the structural data reveal that maspin is able to undergo conformational change in and around the G α-helix, switching between an open and a closed form. This change dictates the electrostatic character of a putative cofactor binding surface and highlights this region as a likely determinant of maspin function. The high resolution crystal structure of maspin provides a detailed molecular framework to elucidate the mechanism of function of this important tumor suppressor.

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Structure of the Ca2+-saturated C-terminal domain of scallop troponin C in complex with a troponin I fragment

Biological Chemistry ◽

10.1515/hsz-2012-0152 ◽

2013 ◽

Vol 394 (1) ◽

pp. 55-68 ◽

Cited By ~ 5

Author(s):

Yusuke S. Kato ◽

Fumiaki Yumoto ◽

Hiroyuki Tanaka ◽

Takuya Miyakawa ◽

Yumiko Miyauchi ◽

...

Keyword(s):

Crystal Structure ◽

Structural Change ◽

Troponin I ◽

Adductor Muscle ◽

Troponin C ◽

Striated Muscles ◽

Terminal Domain ◽

Open Conformation ◽

Ef Hands ◽

Contractile Forces

Abstract Troponin C (TnC) is the Ca2+-sensing subunit of troponin that triggers the contraction of striated muscles. In scallops, the striated muscles consume little ATP energy in sustaining strong contractile forces. The N-terminal domain of TnC works as the Ca2+ sensor in vertebrates, whereas scallop TnC uses the C-terminal domain as the Ca2+ sensor, suggesting that there are differences in the mechanism of the Ca2+-dependent regulation of muscles between invertebrates and vertebrates. Here, we report the crystal structure of Akazara scallop (Chlamys nipponensis akazara) adductor muscle TnC C-terminal domain (asTnCC) complexed with a short troponin I fragment (asTnIS) and Ca2+. The electron density of a Ca2+ ion is observed in only one of the two EF-hands. The EF-hands of asTnCC can only be in the fully open conformation with the assistance of asTnIS. The number of hydrogen bonds between asTnCC and asTnIS is markedly lower than the number in the vertebrate counterparts. The Ca2+ modulation on the binding between asTnCC and asTnIS is weaker, but structural change of the complex depending on Ca2+ concentration was observed. Together, these findings provide a detailed description of the distinct molecular mechanism of contractile regulation in the scallop adductor muscle from that of vertebrates.

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